Table of Contents
Overview
Definition of Gene Expression
Gene expression is defined as the process by which the genetic information encoded in a gene is utilized to produce functional products, primarily proteins or specific RNA molecules. This process is essential for the functioning of living organisms, as it dictates how genes are translated into physical traits and cellular functions.[3.1] Gene expression can be conceptualized as an "on/off switch" that controls when and where RNA molecules and proteins are synthesized, as well as a "volume control" that determines the quantity of these products produced.[5.1] Gene expression is the process by which the genetic information encoded in a gene is utilized to produce functional products, typically proteins or specific RNA molecules.[4.1] In prokaryotic organisms, gene expression is primarily regulated through the control of transcription, which involves synthesizing RNA from DNA. In contrast, eukaryotic cells exhibit a more complex regulation characterized by distinct phases of transcription and translation. In eukaryotes, messenger RNA (mRNA) transcripts are synthesized in the nucleus and subsequently exit to the cytoplasm for translation into proteins.[6.1] The regulation of gene expression can vary depending on the specific gene and cellular context, with various factors influencing this process. For instance, transcription factors are proteins that bind to specific DNA sequences and regulate gene expression.[4.1] Additionally, external signals such as hormones, growth factors, and metabolic cues activate signaling cascades that converge on transcription factors, leading to rapid alterations in gene expression.[21.1] Furthermore, translation initiation factors can also influence gene regulation by controlling the rate of translation initiation, enhancing or inhibiting this process.[20.1] Understanding gene expression is crucial for elucidating biological processes such as development, differentiation, and responses to environmental stimuli, as well as for developing therapeutic strategies to address diseases.[33.1]Importance in Biological Systems
Gene expression is a vital process in living organisms, where genetic information is translated into functional products, primarily proteins or specific RNA molecules. Recent studies have focused on the effects of temperature on gene expression, particularly in ectothermic animals. For instance, research has identified that the 25 genes exhibiting the most significant increase in expression from 25°C to 35°C include seven heat-shock proteins, highlighting the sensitivity of gene expression to temperature changes.[15.1] Additionally, studies on ants have shown that gene expression levels are higher in colder environments, which aligns with findings from fish studies that have predominantly examined the impact of temperature on gene expression in ectotherms.[19.1] These observations underscore the importance of environmental factors, such as temperature, in modulating gene expression and influencing cellular functions across various species. The integration of bioinformatics tools has enhanced our understanding of gene expression by enabling the identification of biological markers for precise diagnosis and the design of targeted therapies.[10.1] These tools facilitate the analysis of gene expression data through pathway enrichment analysis, which identifies biological pathways enriched in differentially expressed genes, thereby linking gene expression to specific biological functions and disease states.[13.1] The integration of bioinformatics with artificial intelligence (AI) and machine learning (ML) has become increasingly significant in the fields of healthcare and biotechnology. Bioinformatics plays a crucial role in gene family analysis, addressing various applications and challenges while paving the way for future innovations in these areas.[12.1] This integration not only enhances our understanding of gene expression patterns but also contributes to advancements in healthcare solutions by overcoming significant hurdles in data management and analysis.[12.1] Through the application of machine learning models, such as logistic regression and random forests, bioinformatics aids in predicting disease risks based on an individual's genomic data, which is essential for the development of personalized medicine.[12.1] In educational contexts, connecting gene expression to its real-world applications is essential for enhancing students' understanding and appreciation of its significance across various fields, including medicine and biotechnology.[25.1] Effective teaching strategies can incorporate engaging methods, interactive tools, and real-world examples to help students grasp complex concepts such as transcription, translation, gene regulation, and mutations.[26.1] Additionally, experiential learning approaches, such as simulations of epigenetic modifications, can deepen comprehension of how gene expression is regulated without altering the DNA sequence, highlighting the importance of modifications like DNA methylation and histone modification in influencing gene activity.[27.1]In this section:
History
Early Discoveries in Genetics
The early discoveries in genetics laid the foundation for our understanding of gene expression. The origins of genetics can be traced back to Gregor Mendel's work on plant hybridization in 1865, which established the principles of heredity. However, the term "genetics" was not introduced until 1906, marking the formal recognition of heredity as a scientific discipline.[60.1] In the early 20th century, Mendelian genetics was integrated with the chromosomal theory of inheritance, proposed by Walter Sutton and Theodore Boveri in 1902, which posited that chromosomes carry genetic material.[58.1] This fusion of ideas led to what is now referred to as "classical genetics," where the gene was understood as a unit of function, transmission, recombination, and mutation.[52.1] During the early twentieth century, significant experiments were conducted to test the validity of Mendel's laws across various organisms. Textbooks from this period included tables of data gathered from these experiments, which highlighted apparent exceptions to Mendel's principles and contributed to the narrative of the development of genetics.[59.1] Gene expression, defined as the spatial and temporal pattern of a gene product, such as mRNA or protein, became a focal point of study during this time.[50.1] Since the early 1960s, scientists have increasingly argued that biological diversity results mainly from changes in gene expression, emphasizing the role of gene regulation as a crucial factor in determining organismal phenotype and evolution.[50.1] However, the widespread recognition of the significance of gene regulation in this context emerged long after the initial synthesis of evolution and genetics.[51.1] The discovery of the structure of DNA in 1953 by James D. Watson and Francis H.C. Crick was a pivotal moment in genetics, as it provided a molecular basis for understanding how genetic information is stored and transmitted.[78.1] This discovery led to the formulation of the central dogma of molecular biology, which describes the flow of genetic information from DNA to RNA to protein.[76.1] The central dogma encapsulates the processes of transcription and translation, which are essential for gene expression, as they convert genetic information into functional products.[75.1]Development of Genetic Techniques
The development of genetic techniques has significantly advanced the field of gene therapy, particularly in the treatment of genetic disorders. One of the primary objectives of these techniques is the modification of genes or adjustment of cell behavior for therapeutic purposes. Recent advancements have focused on gene and cell therapy, emphasizing FDA and EMA-approved therapies and the evolving landscape of genome editing technologies such as CRISPR-Cas9 and viral vectors, which aim to alter or rectify genetic sequences underlying various illnesses.[55.1] Recent advancements in gene therapies have significantly influenced the management of neurologic disorders, providing a comprehensive overview of the mechanisms, challenges, and post-treatment considerations associated with these therapies.[54.1] Several clinical trials are currently underway to address Alzheimer's disease, including a phase I trial that examines the safety and tolerability of Libella gene therapy AAV-hTERT (ClinicalTrials.gov Identifier: NCT04133454) and another trial investigating the continuous delivery of brain-derived neurotrophic factor (BDNF) via AAV2-BDNF to potentially slow or prevent cell loss in individuals with Alzheimer's disease and mild cognitive impairment (ClinicalTrials.gov Identifier: NCT05040217).[57.1] Additionally, a study is evaluating the safety and potential toxicity of directly administering the AAVrh.10hAPOE2 gene transfer vector, which expresses human apolipoprotein E2 (APOE2), into APOE4 homozygotes with Alzheimer's disease (ClinicalTrials.gov Identifier: NCT03634007).[57.1] These ongoing efforts highlight the potential of gene-targeted therapies in addressing specific genetic disorders and improving patient outcomes. Moreover, the integration of next-generation sequencing (NGS) technology has played a crucial role in supporting genomic medicine, facilitating the profiling of gene expression and enhancing the precision of oncogenomics. This has led to a greater need for collaboration between clinicians and researchers to ensure the effective implementation of precision oncology, despite the challenges posed by the complexity of genomic data.[69.1] As gene therapy continues to evolve, discussions surrounding equitable access to these therapies, particularly in low- and middle-income countries, have gained prominence. Events involving international regulatory bodies and healthcare professionals have highlighted the necessity for global collaboration and regulatory innovation to improve access to gene therapies for prevalent diseases such as sickle cell disease.[56.1]Mechanisms Of Gene Expression
Regulation of Gene Expression
Regulation of gene expression encompasses a variety of mechanisms that cells utilize to modulate the production of specific gene products, such as proteins or RNA. This regulation is essential for enabling organisms to adapt to environmental changes, trigger developmental pathways, and maintain cellular differentiation and morphogenesis during embryonic development.[95.1] The regulation of gene expression is a complex process that involves various mechanisms, primarily mediated by transcription factors. These proteins bind to specific DNA sequences and play a crucial role in either activating or repressing gene expression by influencing the binding of RNA polymerase to DNA.[97.1] Transcription factors utilize several mechanisms to regulate gene expression, including stabilizing or blocking RNA polymerase binding, recruiting coactivator or corepressor proteins, and catalyzing modifications to histone proteins, such as acetylation or deacetylation.[92.1] Additionally, DNA methylation can also affect the binding of transcription factors and other regulatory proteins, further modifying gene expression.[91.1] This intricate interplay among transcription factors, promoters, and enhancers is essential for the precise control of gene expression, which is vital for cellular differentiation and the adaptation of organisms to various environmental stimuli.[95.1] Overall, the regulation of gene expression encompasses a wide range of mechanisms that enable cells to modulate the production of specific gene products, thereby enhancing the versatility and adaptability of organisms.[95.1] Epigenetic mechanisms also play a significant role in gene regulation. These mechanisms include DNA methylation, histone modification, and non-coding RNA-associated gene silencing, which can alter gene expression without changing the underlying DNA sequence. For instance, DNA methylation involves the addition of a methyl group to cytosine nucleotides, which can inhibit transcription factor binding and subsequently reduce gene expression.[94.1] Such epigenetic modifications can be influenced by various factors, including age, diet, and environmental stressors.[94.1] During cell differentiation, the regulation of gene expression becomes particularly critical. As stem cells differentiate into specialized cell types, they undergo changes in gene expression patterns governed by a complex gene regulatory network. This network ensures that cells adopt specific phenotypes while maintaining the potential for pluripotency in stem cells.[99.1] The regulation of gene expression during this process is essential for the development of diverse cell types from a common genetic background, highlighting the importance of both intrinsic and extrinsic factors in cellular differentiation.[100.1]In this section:
Recent Advancements
CRISPR and Genome Editing Technologies
The development of CRISPR-based perturbation technologies has the potential to significantly enhance our understanding of gene expression regulation. Specifically, these technologies promise to unlock the language by which gene regulatory elements instruct gene expression, providing insights into the complex mechanisms that govern genetic functions. Additionally, one of the main advantages of profiling the epigenetic state is its ability to compress information within the genome, which may further elucidate the intricacies of gene regulatory functions.[150.1] Recent advancements have integrated CRISPR screens with single-cell omics methodologies, which have greatly improved the study of gene function. Techniques such as PERTURB-seq, CRISP-seq, CROP-seq, and Mosaic-seq utilize single-cell RNA sequencing to track specific guide RNAs (sgRNAs) in individual cells while simultaneously monitoring the full spectrum of gene expression.[151.1] This integration allows researchers to dissect gene regulatory networks with unprecedented resolution. The rapid development of genome-editing tools, including CRISPR, TALENs, and ZFNs, has fundamentally altered biomedical research by providing new methods to accurately edit genomes across various organisms, including humans and pathogens. CRISPR-Cas9, in particular, has been widely adopted for its ability to target and cleave specific DNA or RNA sequences, facilitating applications in biomedicine such as studying host-pathogen interactions, enhancing pathogen resistance, and developing targeted therapies.[152.1] Moreover, CRISPR technology has opened new avenues in gene therapy. The mechanisms by which CRISPR/Cas9 induces gene edits have been elucidated, leading to successful genome editing in mammalian cells. This progress has paved the way for clinical trials utilizing CRISPR gene therapy, although ethical considerations remain a significant aspect of ongoing discussions.[153.1] For instance, exagamglogene autotemcel (exa-cel), the first CRISPR-based therapy to receive regulatory approval, is designed to treat sickle cell disease and transfusion-dependent beta-thalassemia by modifying hematopoietic stem cells to increase fetal hemoglobin levels.[156.1] Furthermore, CRISPR's potential extends beyond traditional gene editing; it is also being explored for epigenetic modifications, which involve altering the chemical structure of DNA without changing the sequence itself. This capability could lead to innovative therapeutic strategies aimed at controlling gene function in a more nuanced manner.[154.1] Overall, the advancements in CRISPR and genome editing technologies are not only enhancing our understanding of gene expression but also holding promise for future therapeutic applications in regenerative medicine and beyond.[155.1]Advances in Gene Expression Profiling Techniques
Recent advancements in gene expression profiling techniques have significantly enhanced our understanding of complex biological systems and diseases. One of the most notable developments is the advent of single-cell transcriptomics, which allows for gene expression analysis at the resolution of individual cells. This technique reveals cellular diversity and dynamic states with unprecedented precision, overcoming limitations associated with bulk RNA sequencing methods that average signals across many cells.[140.1] Additionally, the integration of next-generation sequencing (NGS) technology has revolutionized genomics research by enabling the rapid sequencing of millions of DNA fragments simultaneously. This capability provides comprehensive insights into gene expression profiles, genetic variations, and epigenetic modifications, thereby facilitating studies on various conditions, including rare genetic diseases and cancer.[141.1] The versatility of NGS platforms has expanded the scope of gene expression studies, allowing researchers to analyze complex datasets at an unprecedented depth and scale.[140.1] Moreover, advancements in computational methods have improved data analysis, enabling researchers to capture and interpret gene expression data more effectively. These methods address technical biases that can arise during sequencing, such as differences in RNA capture efficiency and batch effects, ensuring more reliable results.[140.1] Furthermore, the integration of multi-omics approaches is now possible, linking chromatin states, transcriptional regulation, and gene expression into a cohesive framework, which enhances our understanding of the regulatory mechanisms underlying gene expression.[142.1]Applications Of Gene Expression Research
Use in Personalized Medicine
Gene expression research plays a pivotal role in the advancement of personalized medicine, particularly through the development of gene expression signatures that can inform diagnosis and treatment strategies. These signatures, which are specific patterns of gene expression, have shown significant potential in diagnosing various diseases, including infectious and inflammatory conditions. For instance, host blood gene expression signatures have been utilized to identify diseases such as tuberculosis and systemic lupus erythematosus, demonstrating their clinical utility in settings where traditional diagnostics may fall short.[197.1] Moreover, gene expression signatures derived from microarray analysis have been instrumental in prognostic assessments. A notable example is the MammaPrint, a 70-gene expression signature that provides powerful predictions regarding disease outcomes in breast cancer patients.[198.1] This capability to predict disease progression based on gene expression profiles exemplifies the transformative impact of gene expression research on personalized treatment approaches. In the context of infectious diseases, specific gene expression signatures have been developed to differentiate between active and latent tuberculosis, with studies identifying three-gene and 16-gene signatures that predict the risk of active disease.[199.1] Such advancements not only enhance diagnostic accuracy but also facilitate tailored therapeutic interventions, aligning treatment strategies with the unique genetic profiles of individual patients. The integration of gene expression research into personalized medicine has significantly advanced the development of gene therapies and precision medicine, providing new hope for patients facing complex and challenging conditions.[190.1] This progress indicates that gene therapy is likely to play an increasingly important role in the future of medicine.[190.1] Understanding gene expression profiles is essential, as they contribute to the tailoring of effective treatments that can enhance patient outcomes.[190.1]In this section:
Eukaryotic Vs Prokaryotic Gene Expression
Differences in Mechanisms
Prokaryotic and eukaryotic gene expression exhibit significant differences in their mechanisms, primarily due to the structural and functional complexities of the cells involved. In prokaryotic cells, gene expression occurs entirely in the cytoplasm, where transcription and translation happen simultaneously. This is facilitated by the absence of a nucleus, allowing for a direct and rapid response to environmental changes through the regulation of transcription levels alone.[234.1] Conversely, eukaryotic gene expression is more intricate, as it involves distinct compartments within the cell. Transcription occurs in the nucleus, followed by RNA processing, which includes splicing of introns, before the mature mRNA is transported to the cytoplasm for translation.[235.1] The regulation of gene expression varies significantly between prokaryotic and eukaryotic organisms. Prokaryotic cells primarily regulate gene expression by controlling the amount of transcription, as they lack the complex regulatory mechanisms found in eukaryotic cells.[236.1] In contrast, eukaryotic cells exhibit a more intricate regulatory framework that includes multiple levels of control. These levels consist of epigenetic regulation, where DNA is uncoiled and loosened from nucleosomes to allow transcription factors to bind; transcriptional regulation, which occurs during RNA synthesis; post-transcriptional regulation, involving RNA processing and export to the cytoplasm; translational regulation, where RNA is translated into proteins; and post-translational modifications that occur after protein synthesis.[235.1] Furthermore, the compartmentalization of cellular processes in eukaryotes, with transcription occurring in the nucleus and translation in the cytoplasm, allows for a more nuanced control of gene expression compared to prokaryotic cells.[235.1] This increased complexity in eukaryotic gene regulation is a result of evolutionary advancements that have led to the compartmentalization of important cellular components and processes, enhancing the adaptability of these organisms.[236.1] The mechanisms of gene expression in prokaryotes and eukaryotes exhibit significant differences, primarily due to their distinct cellular structures. In prokaryotic cells, gene expression is regulated mainly by controlling the amount of transcription, as they lack introns and the associated splicing processes found in eukaryotic cells.[231.1] Eukaryotic gene regulation, on the other hand, involves the splicing of introns, which is a critical step in the processing of mRNA before it can be translated into proteins.[231.1] This complexity in eukaryotic gene expression is indicative of a more intricate regulatory framework compared to prokaryotes, reflecting the evolutionary advancements that have occurred in eukaryotic organisms.[231.1]Gene Expression Analysis Techniques
Traditional Methods
Traditional methods for gene expression analysis, such as Northern blotting, have significantly contributed to our understanding of gene regulation and function in various biological contexts. Developed in the 1970s, Northern blotting is a classic technique that enables researchers to study RNA molecules, providing crucial insights into gene expression patterns under different conditions. This method is particularly valuable for identifying which genes are active and to what extent, thereby enhancing our knowledge of gene expression dynamics.[293.1] The investigation of gene expression through such foundational techniques plays a vital role in advancing our comprehension of gene regulation across many areas of biology.[309.1] Despite its historical significance, Northern blotting has notable limitations. The technique requires high-quality RNA that is not degraded, which can be challenging to obtain from certain tissues or for inexperienced practitioners.[291.1] Additionally, Northern blotting is generally less sensitive than newer methods such as nuclease protection assays and RT-PCR, necessitating approximately 100,000 copies of a DNA or RNA sequence for detection.[292.1] Furthermore, it lacks the accuracy of fluorescence-based qRT-PCR, which can lead to nonspecific amplification of probes hybridizing with incorrect mRNA.[294.1] Traditional methods such as Northern blotting and qRT-PCR have significantly influenced gene expression analysis. While qRT-PCR is recognized for its ease of use and widespread acceptance, it is often viewed as less reliable compared to Northern blotting, which is considered a gold standard in certain contexts.[295.1] Northern blotting offers unique advantages, including the ability to provide information on the expression level and native size of RNA. Additionally, it allows for direct quantitation of signals, resulting in highly valid expression data.[312.1] This method not only detects the presence of transcripts but also facilitates a relative comparison of transcript abundance on a single membrane, reinforcing its relevance in gene expression studies.[313.1] Thus, despite the advancements in gene expression analysis techniques, traditional methods like Northern blotting continue to play a crucial role in the field.Modern High-Throughput Techniques
Modern high-throughput techniques in gene expression analysis have revolutionized the field by enabling the simultaneous assessment of thousands of genes, thus providing a comprehensive view of gene activity across various biological contexts. Among these techniques, RNA sequencing (RNA-Seq) and microarrays are prominent methods that allow for quantitative measurement of gene expression levels. RNA-Seq, in particular, captures data at unprecedented depth and scale, facilitating the analysis of gene expression at the resolution of individual cells through advancements such as single-cell transcriptomics. This approach reveals cellular diversity and dynamic states with remarkable precision, overcoming limitations associated with traditional methods.[288.1] Microarrays, another cornerstone of high-throughput gene expression analysis, utilize oligonucleotide probes to assess the expression levels of thousands of genes simultaneously. However, the analysis of microarray data is complex and requires sophisticated methods to control for various inherent factors, such as probe design and annotation accuracy. These factors can significantly impact the reliability of the results obtained.[286.1] Despite these challenges, microarrays have been suggested as diagnostic tools in molecular disease classification, necessitating rigorous validation of their accuracy, sensitivity, and reproducibility.[282.1] Modern high-throughput techniques, such as RNA sequencing (RNA-Seq) and microarrays, have revolutionized gene expression profiling by enabling researchers to capture data at unprecedented depth and scale. However, these techniques are not without challenges; they are subject to technical biases, including differences in sequencing depth, RNA capture efficiency, and batch effects, which can affect the reliability of the findings.[288.1] Accurate measurements of absolute expression levels and the reliable detection of low-abundance genes remain difficult to achieve, primarily due to sub-optimal probe design and incorrect probe annotations.[283.1] To address these issues, well-designed data-analysis approaches are essential, as they can help rectify some of the problems associated with gene expression data.[283.1] As the field continues to advance, the integration of innovative computational methods with experimental techniques will enhance the capabilities of gene expression profiling, making it an invaluable resource in biomedical research.[288.1]Epigenetics And Gene Expression
Impact of Epigenetic Modifications
Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome without modifying the DNA sequence itself.[315.1] The term "epigenetics" derives from the Greek prefix "epi," meaning "on top of" or "in addition to" genetics.[314.1] The collection of epigenetic marks within a cell or organism is referred to as its epigenome.[314.1] Three primary mechanisms of epigenetic modification have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing.[315.1] These modifications can be influenced by various factors, including age, diet, smoking, stress, and disease state.[315.1] Importantly, epigenetic changes play a significant role in the regulation of gene expression, impacting numerous biological processes and contributing to the development of various human disorders and diseases.[318.1] For instance, research has shown that prenatal and early postnatal environmental factors can affect the risk of chronic diseases and behavioral disorders in adulthood.[318.1] The control of gene expression is fundamental to cellular differentiation and development, as it accounts for the diverse functions of various cell types despite their identical genetic material.[317.1] Epigenetic processes, including DNA methylation, histone modification, and various RNA-mediated processes, are thought to influence gene expression primarily at the transcriptional level, although they may also regulate other stages of gene expression, such as translation.[317.1] Lineage-specific epigenetic modifications, such as the methylation of the Elf5 promoter, lead to the restriction of transcriptional circuits, which is essential for determining the fate of stem cells during embryonic development.[319.1] Over time, undifferentiated stem cells establish a specific epigenetic profile with the assistance of chromatin-modifying enzymes, which is crucial for their differentiation into various cell types.[320.1] Furthermore, dynamic chromatin accessibility plays a vital role in regulating stem cell fate determination and maintaining tissue homeostasis, with the Polycomb repressive complex 2 (PRC2) serving as a key histone-modifying enzyme that targets developmental regulators during stem cell differentiation.[321.1] Environmental factors, particularly diet and stress, play a significant role in influencing epigenetic modifications and, consequently, gene expression. Research indicates that nutrition is one of the most studied epigenetic factors, with evidence showing that dietary components can trigger epigenetic changes throughout an individual's lifespan, especially during critical developmental windows such as fetal development and early neonatal growth.[322.1] Additionally, the impact of diet on epigenetic modifications is also observed in adult individuals during periods of dietary transitions, underscoring the importance of nutrition at various life stages.[324.1] Chronic stress has been linked to alterations in the epigenetic regulation of genes, including the glucocorticoid receptor gene, which is associated with the development of mental health disorders such as depression and anxiety.[325.1] Furthermore, the interplay between genetic background and environmental factors is crucial in shaping diet-gene interactions, emphasizing the complexity of epigenetic regulation.[324.1] Overall, these findings illustrate how environmental factors, including diet and stress, modulate epigenetic marks, leading to alterations in gene expression patterns and enabling organisms to adapt to their environments.[326.1]In this section:
Future Directions In Gene Expression Research
Emerging Technologies
Emerging technologies in gene expression research are paving the way for significant advancements in understanding and manipulating gene activity. One of the most notable innovations is the application of RNA sequencing (RNA-seq), which provides a comprehensive view of gene expression alterations and has been instrumental in identifying novel transcript species, including long non-coding RNAs and enhancer RNAs. These discoveries contribute to a deeper understanding of epigenetic regulation and the complexities of gene expression dynamics.[363.1] Furthermore, RNA-seq enables researchers to explore alternative promoter usage, mRNA isoforms, and allele-specific expression, which are critical for elucidating disease mechanisms, particularly in cancer.[363.1] Recent advancements in gene expression profiling have significantly enhanced the sensitivity and throughput of studies, allowing for the analysis of gene expression at the single-cell level. This capability enables researchers to capture data at unprecedented depth and scale, revealing cellular diversity and dynamic states with remarkable precision.[355.1] Transcriptomic analyses, such as RNA sequencing, provide a global view of gene expression alterations, which is crucial for identifying potential therapeutic targets and off-target effects.[354.1] Furthermore, by understanding and manipulating the factors that influence gene expression, researchers can achieve high levels of protein production, facilitating advances in biotechnology, medicine, and industrial applications.[353.1] The integration of computational tools and machine learning for predictive modeling is emerging as a vital direction in gene expression research, enabling the design of customized genetic elements that can be precisely controlled and optimized for specific applications.[353.1] Future directions in this field include the continued development of genome editing tools like CRISPR/Cas9 and the application of synthetic biology techniques, which promise to expand the possibilities for gene cloning and expression optimization.[353.1] Moreover, the development of genome editing technologies, such as CRISPR/Cas9, continues to revolutionize gene expression research by allowing precise modifications to the genome. This not only enhances the understanding of gene function but also opens new avenues for applications in biotechnology and medicine.[353.1] The combination of these technologies is expected to drive future research directions, particularly in the fields of precision medicine and agricultural biotechnology, where gene-edited crops can be developed to exhibit desirable traits such as drought tolerance and pest resistance.[356.1]Potential for Therapeutic Applications
Recent advancements in the understanding of gene expression regulation have highlighted the complexity and orchestration of various mechanisms that cells employ to modulate the production of specific gene products, including proteins and RNA.[395.1] This regulation is crucial for numerous biological functions, such as triggering developmental pathways, responding to environmental stimuli, and facilitating cellular differentiation in multicellular organisms.[395.1] Moreover, DNA methylation is known to influence the binding of transcription factors and other regulatory proteins to DNA, thereby modifying gene expression.[392.1] Understanding these regulatory mechanisms is essential for unraveling the complexities of life and developing innovative therapeutic strategies to combat diseases, including neurodegenerative disorders like Alzheimer's disease.[394.1] In the context of Alzheimer's disease, research has identified significant areas of interest, such as long non-coding RNAs, microRNAs, and single nucleotide polymorphisms, which may play critical roles in the disease's biological regulatory mechanisms.[397.1] Emerging research underscores the significant potential of biomarkers in the diagnosis and monitoring of neurodegenerative diseases, particularly focusing on serum microRNAs (miRNAs) and blood cell-derived miRNAs. These biomarkers are being explored as promising non-invasive diagnostic tools for conditions such as Parkinson's disease (PD) and glioblastoma, owing to their remarkable tissue specificity, early appearance, and stability in biological fluids.[389.1] Furthermore, these circulating biomarkers facilitate real-time disease monitoring and have been successfully utilized in the early detection of Alzheimer's disease (AD), PD, and multiple sclerosis (MS).[390.1] Notably, advancements in biomarkers, including cerebrospinal fluid (CSF) and genetic markers, alongside developments in artificial intelligence and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders.[388.1] The integration of these advanced biomarkers into clinical practice is expected to improve diagnostic tools and therapeutic interventions, indicating a promising future for their application in clinical settings.[388.1] Overall, miRNAs are increasingly recognized as significant blood biomarkers for neurodegenerative diseases, highlighting their potential in the diagnosis and prognosis of PD.[391.1] Understanding the molecular mechanisms that regulate gene expression is crucial for developing innovative therapeutic strategies to combat various diseases. The regulation of gene expression is a complex and highly orchestrated process that involves a multitude of key factors and mechanisms, including DNA sequence information, epigenetic modifications, and transcription machinery.[393.1] This complexity is particularly pronounced in eukaryotic systems compared to prokaryotic ones, where transcription initiation serves as the main control point for gene expression.[393.1] Recent advances in transcriptomic studies and computational analyses have enhanced our understanding of how these regulatory mechanisms cooperate, leading to the identification of novel biomarkers and therapeutic targets for human disorders.[396.1] By elucidating these intricate processes, researchers can develop new strategies that not only address the symptoms of diseases but also target their underlying molecular pathways.[394.1]In this section:
Long Non-coding RNAsDisease MechanismsTherapeutic TargetsOff-target EffectsPredictive Modeling
References
[3] Gene Regulation - An overview of Gene Expression and Regulation - BYJU'S — During gene expression, genetic codes from the DNA code are converted into a protein with the help of translation and transcription. The genetic expression shows the process of the genetic makeup of an organism as its physical traits. In this process, the information flows from genes to proteins.
[4] What is Gene Expression? - Definition, Stages, Importance — Gene expression is the process by which the genetic information encoded in a gene is used to produce a functional product, typically a protein or a specific RNA molecule. In prokaryotes, the control of gene expression is primarily achieved through the regulation of transcription, which is the process of synthesizing RNA from DNA. Transcription factors are proteins that bind to specific DNA sequences and regulate gene expression. The addition of methyl groups to DNA can lead to gene silencing, chromatin compaction, interference with transcription factor binding, and DNA instability, all of which contribute to the regulation of gene expression patterns in various biological processes and cell types.
[5] Gene Expression - National Human Genome Research Institute — Gene Expression Scan to visit Skip to main content Skip to navigation Skip to search Skip to slider Skip to about Skip to subscription Skip to footer About Genomics About Genomics* Introduction to Genomics Educational Resources Policy Issues in Genomics The Human Genome Project Research Funding Research Funding* Funding Opportunities Funded Programs & Projects Division and Program Directors Scientific Program Analysts Contacts by Research Area News & Events Research at NHGRI Research at NHGRI* Research Areas Research Investigators Research Projects Clinical Research Data Tools & Resources News & Events About Health About Health* Genomics & Medicine Family Health History For Patients & Families For Health Professionals Careers & Training Careers & Training* Jobs at NHGRI Training at NHGRI Funding for Research Training Professional Development Programs NHGRI Culture News & Events News & Events* News Events Social Media Broadcast Media Image Gallery Videos Press Resources About NHGRI About NHGRI* Organization NHGRI Director Mission and Vision Policies and Guidance Budget Institute Advisors Strategic Vision Leadership Initiatives Inaccessible Partner with NHGRI Staff Search Contact Us Breadcrumb Home About Genomics Educational Resources Talking Glossary of Genomic and Genetic Terms Gene Expression Home About Genomics Educational Resources Talking Glossary of Genomic and Genetic Terms En Español Gene Expression updated: February 7, 2025 Definition Gene expression is the process by which the information encoded in a gene is turned into a function. This mostly occurs via the transcription of RNA molecules that code for proteins or non-coding RNA molecules that serve other functions. Gene expression be thought of as an “on/off switch” to control when and where RNA molecules and proteins are made and as a “volume control” to determine how much of those products are made. The process of gene expression is carefully regulated, changing substantially under different conditions and cell types. The RNA and protein products of many genes serve to regulate the expression of other genes.
[6] Gene Expression - The Definitive Guide - Biology Dictionary — Gene expression in eukaryotes (cells with DNA inside a nucleus) and prokaryotes (single-celled organisms without a nucleus) describes how certain proteins are manufactured in specific cells according to a DNA-based recipe. Copies are made of gene sequences on a strand of DNA by messenger RNA (mRNA); in eukaryotes, these ‘transcripts’ then leave the cell nucleus. So if you are asked, “What is gene expression?”, you need to talk about protein and polypeptide synthesis according to a specific gene found in DNA that has been turned on for that particular cell. While eukaryotic cells have distinct transcription and translation phases inside and outside of the nucleus respectively, gene expression in prokaryotes happens almost in a single phase. Gene expression analysis describes how scientists study gene transcription and translation to form RNA and functional proteins.
[10] Bioinformatics in Gene and Genome Analysis | SpringerLink — Besides, gene and genome analysis also provides information for the detection of biological markers for precise diagnosis and biological targets for drug design (Lazaridis et al. 2014). Bioinformatics has been an important bridge between gene and genome data and the interpretation for clinical applications (Pereira et al. 2020). Bioinformatics
[12] Understanding Bioinformatics and Its Role in Gene Family Analysis — This article explores the significance of bioinformatics in gene family analysis, its applications, challenges, and future prospects, including the integration of AI and machine learning. Discover how bioinformatics contributes to innovations in healthcare and biotechnology while overcoming significant hurdles in data management and analysis.
[13] Differential gene expression analysis pipelines and bioinformatic tools ... — Pathway enrichment analysis is a computational tool to identify biological pathways or pathways significantly enriched in differentially expressed genes/proteins, or associated with a defined set of samples and/or diseases. WikiPathways KEGG (Kyoto Encyclopaedia of Genes and Genomes) , GO (Gene Ontology) , Reactome , STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) , Panther Pathways , , Biocarta , and HumanCyc are some of the most widely used databases, which provide information on metabolic pathways, biological processes, and protein interactions useful to analyze gene expression data and identify pathways and biological functions associated with genes of interest (Table 3).
[15] Effects of temperature on transcriptome and cuticular hydrocarbon ... — To further explore temperature effects on gene expression, we examined those genes with the greatest overall change in expression. The 25 genes with the greatest increase in expression from 25 to 35°C included seven heat‐shock proteins, including six of the 12 genes with the greatest increase in expression (Table S4).
[19] Survival and gene expression under different temperature and humidity ... — The effect of temperature on the gene expression of ectotherm animals has been studied mostly in fish [e.g. 36,37], but less in insects. Our results with ants agree with these studies, and show higher gene expression levels in the colder environment. In contrast, the direct influence of environmental humidity on the level of gene expression is
[20] Factors influencing gene expression and activation - Genetics — The factors that influence gene expression can vary depending on the specific gene and cellular context. Some common factors that can affect gene expression include: ... One way translation initiation factors influence gene regulation is by controlling the rate of translation initiation. They can enhance or inhibit the initiation process
[21] Gene Regulation in Eukaryotes: Mechanisms and Complexities — External signals also influence genome-wide gene regulation. Hormones, growth factors, and metabolic cues activate signaling cascades that converge on transcription factors, rapidly altering gene expression. The glucocorticoid receptor, for example, regulates immune function and glucose metabolism.
[25] 5 Exciting Ways to Teach Gene Expression and Regulation — 5. Connect Gene Expression to its Real-World Applications. Gene expression and regulation have profound implications in various fields, from medicine to biotechnology. Highlight the real-world applications to pique students' curiosity and demonstrate their relevance. For example, discuss how gene expression influences the development of
[26] How to Teach Gene Expression & Protein Synthesis: A Step-by-Step Guide ... — Learn effective strategies for teaching gene expression and protein synthesis with this comprehensive guide. Discover engaging methods, interactive tools, real-world examples, and visual aids to help students understand transcription, translation, gene regulation, and mutations. Perfect for biology
[27] Exploring Gene Expression Mechanisms: Interactive Activities — This experiential learning approach fosters a deeper comprehension of gene regulation processes. Epigenetic Modification Simulations. Epigenetics explores how gene expression can be regulated without altering the DNA sequence. Modifications like DNA methylation and histone modification can alter chromatin structure and influence gene activity.
[33] Gene Regulation: Key Elements in Transcription - BiologyInsights — Understanding gene regulation provides insights into biological processes such as development, differentiation, and response to environmental stimuli. The mechanisms of transcription involve various elements that regulate gene expression, including enhancers, promoters, silencers, insulators, transcription factors, coactivators, and corepressors.
[50] Evolution of Gene Expression - Oxford Bibliographies — Introduction. Gene expression is the spatial and temporal pattern of a gene product, such as mRNA or protein. Since the early 1960s, multiple scientists have argued that biological diversity results mainly from changes in gene expression.
[51] The genetic basis of evolutionary change in gene expression levels - PMC — The regulation of gene expression is an important determinant of organismal phenotype and evolution. However, the widespread recognition of this fact occurred long after the synthesis of evolution and genetics. Here, we give a brief sketch of thoughts regarding gene regulation in the history of evolution and genetics.
[52] From Mendel to epigenetics: History of genetics - PubMed — In the 1910s, Mendelian genetics fused with the chromosomal theory of inheritance, giving rise to what is still called 'classical genetics'. Within this framework, the gene is simultaneously a unit of function and transmission, a unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene coincided.
[54] Current Advances and Challenges in Gene Therapies for Neurologic Disorders — Current Advances and Challenges in Gene Therapies for Neurologic Disorders A Review for the Clinician. ... This article provides a comprehensive overview of gene-targeted therapies currently available for neurologic disorders, with a focus on their mechanisms, challenges, and post-treatment considerations. ... is an X-linked recessive genetic
[55] Targeted Gene Therapy: Promises and Challenges in Disease Management ... — Targeted gene therapy, which involves precise genetic manipulations, heralds a new era in the management of illness. With the use of cutting-edge molecular technologies such as CRISPR-Cas9 and viral vectors, the aim of this therapeutic strategy is to alter or rectify certain genetic sequences that underlie a variety of illnesses [].Targeted gene therapy has great potential to provide
[56] Scientific Advancements in Gene Therapies: Opportunities for ... - MDPI — The event brought together a diverse group of experts, including international regulatory bodies, regulated industries, healthcare professionals, patients, academic researchers and global health advocates, to discuss the rapid advancements in gene therapy and the pressing need for equitable access in low-and middle-income countries (LMICs), with sickle cell disease (SCD) serving as the model disorder for the discussions. Opening remarks provided by Dr. Peter Marks from the FDA Center for Biologics Evaluation and Research, Dr. Julie Makani from the Muhimbili University of Health and Allied Sciences and Dr. Mike McCune from the Gates Foundation emphasized that the need for global collaboration, equitable access and regulatory innovation to make gene therapies better available to patients in LMICs, particularly for highly prevalent diseases such as SCD.
[57] Current developments of gene therapy in human diseases - PMC — 173 Several other clinical trials are ongoing to address Alzheimer's disease, including a phase I trial examining the safety and tolerability of Libella gene therapy AAV‐hTERT (ClinicalTrials.gov Identifier: NCT04133454), a phase I trial examining whether continuously delivering brain‐derived neurotrophic factor (BDNF) into the brain by AAV2‐BDNF can slow or prevent cell loss in individuals with Alzheimer's disease and mild cognitive impairment (ClinicalTrials.gov Identifier: NCT05040217), and a study evaluating the safety and potential toxicity of directly administering AAVrh.10hAPOE2 (LX1001) gene transfer vector expressing human apolipoprotein E2 (APOE2) into APOE4 homozygotes with Alzheimer's disease (ClinicalTrials.gov Identifier: NCT03634007).
[58] History of Genetics By Year | DNA History | BioExplorer — During the 20th Century To Current At the start of the 20th century, The works of Mendel were rediscovered by three scientists, namely Carl Correns, Hugo de Vries, and Erik Tschermak. 1902: Walter Sutton and Theodore Boveri postulated the Chromosomal theory ( PDF ) which describes that chromosomes carry the cell's genetic material (gene).
[59] Principles, exemplars, and uses of history in early 20th century ... — Textbooks also included tables of data gathered in early twentieth-century experiments testing the validity of Mendel's laws on other organisms. 38 These tables were used as part of the narrative by which the student experienced the development of the science, discovering apparent exceptions to Mendel's principles and finding ways of
[60] From Mendel to epigenetics: History of genetics - ScienceDirect — La génétique puise ses origines dans le mémoire de Mendel sur l’hybridation des plantes (1865). Le mot « génétique » ne fut cependant introduit qu’en 1906 pour désigner la nouvelle science de l’hérédité. Fondée sur la méthode mendélienne d’analyse des produits de croisements, cette science se distingue par son but explicite — être une science générale de l’hérédité —, et par l’introduction de concepts biologiques totalement nouveaux (notamment ceux de gène, de génotype et de phénotype). Dans les années 1910, la génétique mendélienne a fusionné avec la théorie chromosomique de l’hérédité pour donner ce qu’on appelle toujours aujourd’hui la « génétique classique ». For all open access content, the Creative Commons licensing terms apply.
[69] Navigating ethical challenges of integrating genomic medicine into ... — The development of gene expression profiling and next-generation sequencing technologies have steered oncogenomics to the forefront of precision medicine. This created a need for harmonious cooperation between clinicians and researchers to increase access to precision oncology, despite multiple implementation challenges being encountered.
[75] 4.1: Central Dogma of Molecular Biology - Biology LibreTexts — The central dogma of molecular biology states that DNA contains instructions for making a protein, which are copied by RNA. RNA then uses the instructions to make a protein.
[76] Central Dogma - Steps Involved in Central Dogma - BYJU'S — In molecular biology, central dogma illustrates the flow of genetic information from DNA to RNA to protein. It is defined as a process in which the information in DNA is converted into a functional product.
[78] Chemical structure of DNA discovered | February 28, 1953 - HISTORY — On February 28, 1953, Cambridge University scientists James D. Watson and Francis H.C. Crick announce that they have determined the double-helix structure of DNA, the molecule containing human genes.
[91] Regulation of Gene Expression: An Overview of Mechanisms and Processes — Moreover, DNA methylation can also regulate the binding of transcription factors and other regulatory proteins to DNA, thereby modifying gene expression. While transcriptional regulation, involving the activities of transcription factors, enhancers, and promoters, plays a crucial role in controlling gene expression, post-transcriptional modifications also contribute to the fine-tuning of gene expression. Promoters contain specific DNA sequences that serve as binding sites for transcription factors, proteins that regulate gene expression. In addition to the general mechanisms of gene expression regulation, such as promoters, transcription factors, and epigenetic modifications, there is another level of control called genomic imprinting. Overall, the regulation of gene expression through DNA transcription involves a complex interplay of repressors, promoters, enhancers, and transcription factors. Transcription factors are proteins that bind to specific DNA sequences and either activate or repress gene expression.
[92] Chapter 6. Mechanisms of Gene Expression - Human Genetics — Transcription factors use a variety of mechanisms for the regulation of gene expression. These mechanisms include: Stabilize or block the binding of RNA polymerase to DNA. Recruit coactivator or corepressor proteins to the transcription factor DNA complex. Catalyze the acetylation or deacetylation of histone proteins.
[94] Genetics, Epigenetic Mechanism - StatPearls - NCBI Bookshelf — Introduction Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome rather than in the DNA sequence. Despite not directly altering the DNA sequence, epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure in which DNA is packaged. These epigenetic modifications can be induced by several factors including age, diet, smoking, stress, and disease state. Three different epigenetic mechanisms have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Catalyzed by DNA methyltransferase enzymes, DNA methylation involves the addition of a methyl group directly to a cytosine nucleotide within a cytosine-guanine sequence (CpG), which are often surrounded by other CpG’s forming a CpG island.
[95] Regulation of gene expression - Wikipedia — Regulation of gene expression by a hormone receptor Diagram showing at which stages in the DNA-mRNA-protein pathway expression can be controlled Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. In multicellular organisms, gene regulation drives cellular differentiation and morphogenesis in the embryo, leading to the creation of different cell types that possess different gene expression profiles from the same genome sequence.
[97] 16.14: Regulating Gene Expression in Cell Development - Mechanics of ... — Figure \(\PageIndex{1}\): Transcription Factors Regulate Gene Expression: While each body cell contains the organism's entire genome, different cells regulate gene expression with the use of various transcription factors. Transcription factors are proteins that affect the binding of RNA polymerase to a particular gene on the DNA molecule.
[99] Regulation of Gene Expression in Cell Differentiation — Understanding how gene expression is regulated during cell differentiation is crucial for grasping the remarkable diversity of cell types in multicellular organisms. This process involves complex interactions and finely tuned mechanisms that ensure cells develop specialized functions from a common origin. In research and medicine, insights into these regulatory pathways can lead to advances in
[100] Gene Expression Regulates Cell Differentiation - Nature — This page has been archived and is no longer updated Gene Expression Regulates Cell Differentiation All of the cells within a complex multicellular organism such as a human being contain the same DNA; however, the body of such an organism is clearly composed of many different types of cells. In other words, the particular combination of genes that are turned on (expressed) or turned off (repressed) dictates cellular morphology (shape) and function. This process of gene expression is regulated by cues from both within and outside cells, and the interplay between these cues and the genome affects essentially all processes that occur during embryonic development and adult life. This fascinating demonstration has led to the proposal that changes in gene expression, rather than losses of genetic material, play a key role in guiding and maintaining cell differentiation.
[140] Gene Expression Profiling: Advances, Techniques, and Analysis — Gene Expression Profiling: Advances, Techniques, and Analysis - BiologyInsights Gene Expression Profiling: Advances, Techniques, and Analysis Explore the latest advances in gene expression profiling, from experimental techniques to data analysis, and their impact on biological research. With new experimental techniques and computational methods, gene expression studies can now capture data at unprecedented depth and scale. Advancements in gene expression profiling have led to multiple experimental techniques, each offering distinct advantages in sensitivity, throughput, and spatial resolution. Single-cell transcriptomics overcomes this limitation by enabling gene expression analysis at the resolution of individual cells, revealing cellular diversity and dynamic states with unprecedented precision. Gene expression data is subject to technical biases, including differences in sequencing depth, RNA capture efficiency, and batch effects.
[141] Next-Generation Sequencing Technology: Current Trends and Advancements — Abstract The advent of next-generation sequencing (NGS) has brought about a paradigm shift in genomics research, offering unparalleled capabilities for analyzing DNA and RNA molecules in a high-throughput and cost-effective manner. This transformative technology has swiftly propelled genomics advancements across diverse domains. NGS allows for the rapid sequencing of millions of DNA fragments simultaneously, providing comprehensive insights into genome structure, genetic variations, gene expression profiles, and epigenetic modifications. The versatility of NGS platforms has expanded the scope of genomics research, facilitating studies on rare genetic diseases, cancer genomics, microbiome analysis, infectious diseases, and population genetics. This review provides an insightful overview of the current trends and recent advancements in NGS technology, highlighting its potential impact on diverse areas of genomic research.
[142] Profiling the epigenome using long-read sequencing — These advancements are now facilitating the integration of multi-omics approaches, linking chromatin states, transcriptional regulation and gene expression in a single, cohesive framework.
[150] A CRISPR view of gene regulation - PMC — All in all, CRISPR-based perturbation promises to unlock the language by which gene regulatory elements instruct gene expression. How best to "compress" gene regulatory function One of the main promises of profiling epigenetic state is to compress information in the genome.
[151] Past, present, and future of CRISPR genome editing technologies — The integration of CRISPR screens with single-cell omics methodologies has greatly enhanced our ability to study gene function. 237 Methods like PERTURB-seq, 252 CRISP-seq, 239 CROP-seq, 238 and Mosaic-seq 253 use single-cell RNA sequencing to track sgRNAs in individual cells and simultaneously monitor the full spectrum of gene expression
[152] The CRISPR revolution and its potential impact on global health ... — The rapid development of genome-editing tools, including TALENs, ZFNs, and CRISPR-Cas, that are able to programmatically target highly specific sequences of DNA or RNA provide a powerful new method of addressing global health challenges . CRISPR-Cas in particular has become widely used for specific targeting and cleavage of DNA or RNA, with many potential applications in biomedicine including studying the host–pathogen relationship, editing the host genome for pathogen resistance, detecting pathogens, and directly targeting pathogens for therapeutic purposes . The recent development of genome-editing technologies, including TALENs , ZFNs , and CRISPR-Cas , has fundamentally changed the direction of biomedical research by providing new tools that can accurately edit an organism’s genome, which may belong to a human, pathogen, or animal model.
[153] CRISPR Gene Therapy: Applications, Limitations, and Implications for ... — This review aims to (1) provide a brief history of gene therapy prior to CRISPR and discuss its ethical dilemmas, (2) describe the mechanisms by which CRISPR/Cas9 induces gene edits, (3) discuss the current limitations and advancements made for CRISPR technology for therapeutic translation, and (4) highlight a few recent clinical trials utilizing CRISPR gene therapy while opening a discussion for the ethical barriers that these and future trials may hinge upon. This was followed by studies demonstrating successful genome editing by CRISPR/Cas9 in mammalian cells, thereby opening the possibility of implementing CRISPR/Cas9 in gene therapy (29) (Figure 1). | Crispr Therapeutics | B-cell MalignancyNon-Hodgkin LymphomaB-cell Lymphoma | TCRα, TCRβ | NCT04035434 | CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components) |
[154] What is CRISPR? A bioengineer explains | Stanford Report — Here, Stanford University bioengineer Stanley Qi explains how CRISPR works, why it’s such an important tool, and how it could be used in the future – including current developments in using CRISPR to edit the epigenome, which involves altering the chemistry of DNA instead of the DNA sequence itself. ```The short answer: CRISPR can precisely modify a piece of DNA or its chemistry (so-called epigenetics) in the human body, making it a potential tool for clinical uses in the biomedical sciences. ```The short answer: In about a decade, scientists went from wondering if this technology would even work in human cells to getting the first CRISPR drug approved uses in the clinic. ```The short answer: We’re trying to use CRISPR to control gene function rather than editing genes to treat diseases.
[155] CRISPR innovations in tissue engineering and gene editing — CRISPR innovations in tissue engineering and gene editing - ScienceDirect Search ScienceDirect CRISPR innovations in tissue engineering and gene editing open access The CRISPR/Cas9 system is a powerful tool for genome editing, utilizing the Cas9 nuclease and programmable single guide RNA (sgRNA). We also explore their applications in stem cell engineering and regenerative medicine, with a focus on in vitro stem cell fate manipulation and in vivo treatments. Furthermore, we discuss the challenges of translating CRISPR technologies into regenerative medicine and provide future perspectives. Overall, this review highlights the potential of CRISPR in advancing regenerative medicine and offers insights into its application in various areas of research and therapy. Next article in issue No articles found. For all open access content, the relevant licensing terms apply.
[156] CRISPR Technologies for In Vivo and Ex Vivo Gene Editing — Exagamglogene autotemcel (exa-cel), sold under the brand name Casgevy, is the first and only CRISPR-based therapy to receive regulatory approval anywhere internationally.6,7 Exa-cel is a CRISPR Cas9 gene-editing therapy intended to treat certain people with sickle cell disease or transfusion-dependent beta-thalassemia.1,8 (At the time of writing, exa-cel is undergoing reimbursement review by Canada’s Drug Agency for both sickle cell disease and transfusion-dependent beta-thalassemia.) Exa-cel uses CRISPR Cas9–based gene editing to increase the amount of fetal hemoglobin in red blood cells by deleting a portion of the BC11A gene.8 The treatment involves harvesting hematopoietic stem cells from the patient, which are sent to a facility where they are modified using CRISPR Cas9. https://www.newswire.ca/news-releases/health-canada-grants-marketing-authorization-of-first-crispr-cas9-gene-edited-therapy-casgevy-r-exagamglogene-autotemcel-for-the-treatment-of-sickle-cell-disease-and-transfusion-dependent-beta-thalassemia-898047529.html Accessed 2024 Sep 26.
[190] Understanding the Impact of Genetics on Medicine — This has paved the way for the development of gene therapies and precision medicine, offering new hope to patients with complex and challenging conditions. ... gene therapy is likely to play an increasingly important role in the future of medicine. The Impact of Genetic Research. ... medicine, and treatment. Gene Expression and Disease Outcome.
[197] Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene ... — Host blood gene expression signatures have been shown to identify several specific infectious and inflammatory diseases, including tuberculosis, 15 bacterial and viral infections, 16,17 and systemic lupus erythematosus. 18 Support for a diagnostic approach to KD based on gene expression signatures comes from identification of microRNA
[198] A Toolbox for Functional Analysis and the Systematic Identification of ... — Numerous studies demonstrated the clinical usefulness of diagnostic (disease detection) and prognostic (disease outcome) gene-expression signatures derived from microarray analysis . For instance, MammaPrint is a 70 gene-expression prognostic signature for powerful disease outcome prediction in breast cancer .
[199] Discovering transcriptional signatures of disease for diagnosis versus ... — Examples of promising diagnostic tools to discriminate between active and latent TB include a three-gene signature 10, and BATF2 gene expression 6 in whole blood. More recently, a 16‑gene signature in whole blood was reported to predict risk of active disease in individuals with latent TB 7. These signatures may include genes that are dys
[231] Gene expression prokaryotes vs eukaryotes: 7 major differences — Splicing of introns is involved in eukaryotic gene regulation but in prokaryotes, this process is absent as they don't contain introns. ... understanding of gene expression difference between regulation of gene expression in prokaryotes and eukaryotes. This article will help you to understand the core concept of Gene expression prokaryotes vs
[234] Prokaryotic versus Eukaryotic Gene Expression — To understand how gene expression is regulated, we must first understand how a gene becomes a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different fashions. Because prokaryotic organisms lack a cell nucleus, the processes of transcription and translation occur almost simultaneously.
[235] Prokaryotic and Eukaryotic Gene Regulation | Biology for Majors I — Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level), when the RNA is translated into protein (translational level), or after the protein has been made (post-translational level).
[236] 22.2: Gene Expression- Prokaryotes vs. Eukaryotes — Evolution of Gene Regulation. Prokaryotic cells can only regulate gene expression by controlling the amount of transcription. As eukaryotic cells evolved, the complexity of the control of gene expression increased. For example, with the evolution of eukaryotic cells came compartmentalization of important cellular components and cellular processes.
[282] Reliability and reproducibility issues in DNA microarray measurements — However, the stakes were raised when microarrays were suggested as a diagnostic tool in molecular disease classification (Box 2), because regulatory agencies, such as the Food and Drug Adminis tration (FDA), require solid, empirically supported data about the accuracy, sensitivity, specificity, reproducibility and reliability of
[283] Reliability and reproducibility issues in DNA microarray ... - PubMed — However, accurate measurements of absolute expression levels and the reliable detection of low abundance genes are difficult to achieve. The main problems seem to be the sub-optimal design or choice of probes and some incorrect probe annotations. Well-designed data-analysis approaches can rectify some of these problems.
[286] Microarray experiments and factors which affect their reliability — Oligonucleotide microarrays belong to the basic tools of molecular biology and allow for simultaneous assessment of the expression level of thousands of genes. Analysis of microarray data is however very complex, requiring sophisticated methods to control for various factors that are inherent to the procedures used. In this article we describe the individual steps of a microarray experiment
[288] Gene Expression Profiling: Advances, Techniques, and Analysis — Gene Expression Profiling: Advances, Techniques, and Analysis - BiologyInsights Gene Expression Profiling: Advances, Techniques, and Analysis Explore the latest advances in gene expression profiling, from experimental techniques to data analysis, and their impact on biological research. With new experimental techniques and computational methods, gene expression studies can now capture data at unprecedented depth and scale. Advancements in gene expression profiling have led to multiple experimental techniques, each offering distinct advantages in sensitivity, throughput, and spatial resolution. Single-cell transcriptomics overcomes this limitation by enabling gene expression analysis at the resolution of individual cells, revealing cellular diversity and dynamic states with unprecedented precision. Gene expression data is subject to technical biases, including differences in sequencing depth, RNA capture efficiency, and batch effects.
[291] Northern Blot Analysis of Gene Expression | SpringerLink — There are two disadvantages often associated with this technique. The RNA isolated from cells or tissues must be of high quality, not degraded, which can be difficult in some tissues or for inexperienced workers. ... Krumlauf, R. (1991). Northern Blot Analysis of Gene Expression. In: Murray, E.J. (eds) Gene Transfer and Expression Protocols
[292] Northern blots - Pros and Cons - teachline.ls.huji.ac.il — Criteria: Advantages: Limitations: General: The procedure is relatively fast, "low- tech" and cheap. Standard Northern procedure is, in general, less sensitive than nuclease protection assays and RT-PCR.Approximately 100,000 copies of a DNA or RNA sequence are required for detection by blot hybridization.
[293] Northern Blotting (RNA Blotting) - Lab Tests Guide — RNA Analysis: Northern blotting is a classic method developed in the 1970s to study RNA molecules, allowing researchers to gain insights into gene expression. Gene Expression : It is a crucial tool for investigating gene expression patterns under various conditions, providing valuable information about which genes are active and to what extent.
[294] A Comparison Between Northern Blotting and Quantitative Real-Time PCR ... — However, for the study of gene expression patterns, Northern blotting analysis has been replaced by qRT- PCR. In comparison with qRT-PCR, Northern blotting analysis lacks the accuracy of fluorescence-based qRT- PCR and unspecific amplification of the probe hybrid- izes with the wrong mRNA.
[295] Which is more reliable in gene expression analysis, northern blot or rt ... — All in all, although qRT-PCR it's easier to perform than, and more widely largely accepted of northern blot, I personally think that northern blot is more reliable.
[309] Northern blot analysis for detection and quantification of RNA in ... — Investigation of gene expression significantly contributes to our knowledge of the regulation and function of genes in many areas of biology. In this protocol, we describe how northern blot
[312] Modified Northern blot protocol for easy detection of mRNAs in total ... — Northern blot analysis has a unique advantage of providing information on expression level and native size of the RNA, and the direct quantitation of the signal also makes it a technique that provides highly valid expression data, so it is still a widely used technique as a gold standard for the direct study of gene expression at the RNA level
[313] Northern Blotting Technique for Detection and Expression ... - PubMed — Northern analysis is a conventional but gold standard method for detection and quantification of gene expression changes. It not only detects the presence of a transcript but also indicates size and relative comparison of transcript abundance on a single membrane. ... Northern Blotting Technique for Detection and Expression Analysis of mRNAs
[314] Epigenetics and Heritable Control of Gene Expression — Epigenetics is the study of various heritable alterations that control gene expression without changing the DNA sequence. 1 The name epigenetics comes from the Greek prefix "epi", which means on top of, or in addition to, genetics. 2 The collection of epigenetic marks in a cell or organism is known as its epigenome.
[315] Genetics, Epigenetic Mechanism - StatPearls - NCBI Bookshelf — Introduction Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome rather than in the DNA sequence. Despite not directly altering the DNA sequence, epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure in which DNA is packaged. These epigenetic modifications can be induced by several factors including age, diet, smoking, stress, and disease state. Three different epigenetic mechanisms have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Catalyzed by DNA methyltransferase enzymes, DNA methylation involves the addition of a methyl group directly to a cytosine nucleotide within a cytosine-guanine sequence (CpG), which are often surrounded by other CpG’s forming a CpG island.
[317] Epigenetics and gene expression - PubMed — Thus, control of gene expression is at the heart of differentiation and development. Epigenetic processes, including DNA methylation, histone modification and various RNA-mediated processes, are thought to influence gene expression chiefly at the level of transcription; however, other steps in the process (for example, translation) may also be
[318] Epigenetics: Fundamentals, History, and Examples | What is Epigenetics? — At least three systems including DNA methylation, histone modification and non-coding RNA (ncRNA)-associated gene silencing are currently considered to initiate and sustain epigenetic change.1 New and ongoing research is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases. For example, human epidemiological studies have provided evidence that prenatal and early postnatal environmental factors influence the adult risk of developing various chronic diseases and behavioral disorders.5 Studies have shown that children born during the period of the Dutch famine from 1944-1945 have increased rates of coronary heart disease and obesity after maternal exposure to famine during early pregnancy compared to those not exposed to famine.6 Less DNA methylation of the insulin-like growth factor II (IGF2) gene, a well-characterized epigenetic locus, was found to be associated with this exposure.7 Likewise, adults that were prenatally exposed to famine conditions have also been reported to have significantly higher incidence of schizophrenia.89
[319] Epigenetic dynamics of stem cells and cell lineage commitment: digging ... — Lineage-specific epigenetic modification of crucial transcription factor loci (for example, methylation of the Elf5 promoter) leads to the restriction of transcriptional circuits and the fixation
[320] Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy ... — Over time, with the help of chromatin-modifying enzymes, undifferentiated stem cells will establish a specific epigenetic profile to determine cell fate. In fact, these epigenetic modifications are responsible for ESC differentiation into various cell types during embryogenesis . Upon lineage commitment, pluripotent factors are silenced and the
[321] Epigenetic regulation of embryonic ectoderm development in stem cell ... — Dynamic chromatin accessibility regulates stem cell fate determination and tissue homeostasis via controlling gene expression. As a histone‐modifying enzyme that predominantly mediates methylation of lysine 27 in histone H3 (H3K27me1/2/3), Polycomb repressive complex 2 (PRC2) plays the canonical role in targeting developmental regulators during stem cell differentiation and transformation.
[322] The role of nutrition on epigenetic modifications and their ... — It is remarkable to note that current evidence linking diet to epigenetic modifications can be narrowed down to two specific scenarios: First, during "critical windows" of early development (specially during fetal development and/or early neonatal growth) and, second, in adult individuals, during "Dietary Transitions" (such as high fat
[324] How Different Diets Affect Human Epigenetics Throughout Generations — Research on Epigenetics. The role of genetic background in determining dietary responses within a community is widely acknowledged. However, recent scientific evidence suggests that it is not solely genetic factors, but rather a complex interplay between environmental factors and genetic background, that ultimately governs diet-gene interactions (Kaput, J., 2004).
[325] Epigenetics: How Your Environment Changes Your DNA Without Rewriting It — In this article, we will explore the science behind epigenetics, the mechanisms through which it operates, its role in human development and disease, and the ways in which environmental factors shape our genetic destiny. Epigenetics involves chemical modifications to the DNA molecule or its associated proteins, which regulate gene activity without altering the underlying sequence. Disorders such as schizophrenia, depression, and Alzheimer’s disease have been linked to changes in DNA methylation and histone modification in genes related to brain function. For example, studies have shown that chronic stress can alter the epigenetic regulation of the glucocorticoid receptor gene, contributing to the development of depression and anxiety disorders.
[326] Epigenetics: Environmental Impacts on Gene Expression — Epigenetics: Environmental Impacts on Gene Expression - BiologyInsights Epigenetics: Environmental Impacts on Gene Expression Explore how environmental factors influence gene expression through epigenetic modifications, shaping health and development. Epigenetics represents a fascinating dimension of biology, where gene expression is influenced by factors beyond the DNA sequence itself. These modifications shape how genes are expressed without altering the underlying genetic code. Epigenetic modifications are biochemical processes that regulate gene activity without altering the DNA sequence. Various environmental factors such as diet, pollutants, and stressors can modulate epigenetic marks, leading to alterations in gene expression patterns. This interplay between genetic and epigenetic mechanisms ensures that gene expression is precisely controlled, enabling organisms to adapt to new challenges.
[353] Unlocking Genetic Potential: Advances and Applications in Gene Cloning ... — By understanding and manipulating the factors that influence gene expression, researchers can achieve high levels of protein production, facilitating advances in biotechnology, medicine, and industrial applications. In conclusion, the recent advances in gene cloning and expression optimization, driven by technologies such as CRISPR/Cas9, synthetic biology, and high-throughput screening, have opened new avenues for research and applications. These advancements enable the design of customized genetic elements that can be precisely controlled and optimized for specific applications, expanding the possibilities for gene cloning and expression optimization. Future directions in gene cloning and expression optimization include the continued development of CRISPR/Cas9 and other genome editing tools, the integration of computational tools and machine learning for predictive modeling, and the application of synthetic biology techniques.
[354] p300 Inhibitor: Mechanisms, Types, and Future Directions — Transcriptomic analyses, such as RNA sequencing, provide a global view of gene expression alterations, identifying potential therapeutic targets and off-target effects. These methods collectively guide the refinement of p300 inhibitors for clinical applications.
[355] Gene Expression Profiling: Advances, Techniques, and Analysis — Gene Expression Profiling: Advances, Techniques, and Analysis - BiologyInsights Gene Expression Profiling: Advances, Techniques, and Analysis Explore the latest advances in gene expression profiling, from experimental techniques to data analysis, and their impact on biological research. With new experimental techniques and computational methods, gene expression studies can now capture data at unprecedented depth and scale. Advancements in gene expression profiling have led to multiple experimental techniques, each offering distinct advantages in sensitivity, throughput, and spatial resolution. Single-cell transcriptomics overcomes this limitation by enabling gene expression analysis at the resolution of individual cells, revealing cellular diversity and dynamic states with unprecedented precision. Gene expression data is subject to technical biases, including differences in sequencing depth, RNA capture efficiency, and batch effects.
[356] Gene Lab Impact: Genetic Innovations: Startups Disrupting Industries ... — Some of the innovations that are disrupting the agriculture industry through gene research are: - Gene-edited crops: Using tools such as CRISPR-Cas9, researchers can precisely edit the DNA of plants to introduce desirable traits such as drought tolerance, pest resistance, and improved nutrition. For example, a startup called Pairwise is
[363] Advanced Applications of RNA Sequencing and Challenges — Only until recently, it was appreciated that 85% of the human genome can be transcribed, albeit only 3% of the genome encodes protein-coding genes.6 Thus, RNA-seq has been instrumental to catalog the diversity of novel transcript species including long non-coding RNA, miRNA, siRNA, and other small RNA classes (eg, snRNA and piRNA) involved in regulation of RNA stability, protein translation, or the modulation of chromatin states.7,8 For instance, RNA-seq has been used to discover enhancer RNA, a class of short transcript directly transcribed from the enhancer region, which contributes to our knowledge of epigenetic gene regulation.9,10 In addition, RNA-seq can give information about transcriptional start sites, revealing alternative promoter usage, information about mRNA isoforms derived from alternative splicing, and premature transcription termination at the 3′ end, which is critical from mRNA stability.11–15 Most recently, RNA-seq was used to study biological problems including precisely locating regulatory elements.16,17 RNA-seq information can also identify allele-specific expression, disease-associated single nucleotide polymorphisms (SNP), and gene fusions contributing to our understanding about disease causal variants in cancer.18–21 Furthermore, RNA-seq can provide information about the transcription of endogenous retrotransposons and other parasitic repeat elements that may influence the transcription of neighboring genes or may result in somatic mosaicism in the brain.22 Finally, single-cell RNA-seq analysis has been widely applied to study the cellular heterogeneity and diversity in stem cell biology and neuroscience.23–25
[388] Advances in understanding biomarkers and treating neurological diseases ... — Biomarkers, including cerebrospinal fluid (CSF), genetic markers, and advances in AI and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders. Notable advancements include improved diagnostic tools, gene therapy, and novel clinical trials.
[389] Biomarkers in neurodegenerative diseases: a broad overview — More recently, serum miRNAs and blood cell-derived miRNAs are being explored as non-invasive diagnostic biomarkers for PD, glioblastoma, and other diseases [33–35]. In summary, the use of miRNAs in various diseases, including CNS disorders, holds significant potential as biomarkers due to their remarkable tissue specificity, early appearance, and stability in biological fluids. The research on Ng in various neurodegenerative disorders, including AD, PD, Creutzfeldt-Jakob disease (CJD), and HAND, highlights its potential as a biomarker for these conditions. miR-218-5p and miR-320a-5p as biomarkers for brain disorders: focus on the major depressive disorder and Parkinson’s disease. Circulating plasma miR-23b-3p as a biomarker target for idiopathic Parkinson’s disease: comparison with small extracellular vesicle miRNA. Elevated plasma miR-133b and miR-221-3p as biomarkers for early Parkinson’s disease. miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer’s disease.
[390] Molecular Biomarkers in Neurological Diseases: Advances in Diagnosis ... — These circulating biomarkers offer the advantage of real-time disease monitoring and have been successfully utilized in the early detection of AD, PD, and MS. For example, exosomal tau and amyloid-beta peptides have shown diagnostic potential for AD, while plasma α-synuclein and DJ-1 protein levels serve as promising biomarkers for PD.
[391] Biomarkers of Neurodegenerative Diseases: Biology, Taxonomy, Clinical ... — Its high levels can also imply a lower risk and slower progress of the disease, making it a promising biomarker for the diagnosis and prognosis of PD . 9.2. miRNA as Potential PD Biomarkers. miRNA molecules are considered a promising blood biomarker for neurodegenerative diseases.
[392] Regulation of Gene Expression: An Overview of Mechanisms and Processes — Moreover, DNA methylation can also regulate the binding of transcription factors and other regulatory proteins to DNA, thereby modifying gene expression. While transcriptional regulation, involving the activities of transcription factors, enhancers, and promoters, plays a crucial role in controlling gene expression, post-transcriptional modifications also contribute to the fine-tuning of gene expression. Promoters contain specific DNA sequences that serve as binding sites for transcription factors, proteins that regulate gene expression. In addition to the general mechanisms of gene expression regulation, such as promoters, transcription factors, and epigenetic modifications, there is another level of control called genomic imprinting. Overall, the regulation of gene expression through DNA transcription involves a complex interplay of repressors, promoters, enhancers, and transcription factors. Transcription factors are proteins that bind to specific DNA sequences and either activate or repress gene expression.
[393] Regulatory Mechanisms Involved in Gene Expression - News-Medical.net — By Dr. Surat P, Ph.D.Reviewed by Susha Cheriyedath, M.Sc. Gene expression can be regulated by various cellular processes with the aim to control the amount and nature of the expressed genes. This article aims to describe the regulatory mechanisms that control gene expression in both eukaryotes and prokaryotes. The regulation of gene expression is more complex in eukaryotes than in prokaryotes. Regulating Gene Expression This is a key point of regulation of eukaryotic gene expression. This step is a key point of regulation of gene expression in eukaryotes. Regulation of Gene Expression in Prokaryotes In prokaryotes, transcription initiation is the main point of control of gene expression. All Gene Expression Content Retrieved on March 01, 2025 from https://www.news-medical.net/life-sciences/Regulatory-Mechanisms-Involved-in-Gene-Expression.aspx. <https://www.news-medical.net/life-sciences/Regulatory-Mechanisms-Involved-in-Gene-Expression.aspx>. https://www.news-medical.net/life-sciences/Regulatory-Mechanisms-Involved-in-Gene-Expression.aspx. News-Medical, viewed 01 March 2025, https://www.news-medical.net/life-sciences/Regulatory-Mechanisms-Involved-in-Gene-Expression.aspx.
[394] Regulation of Gene Expression: Key Factors and Mechanisms - Genetics — In conclusion, the regulation of gene expression is a complex and highly orchestrated process that involves a multitude of key factors and mechanisms. Understanding these regulatory mechanisms is essential for unraveling the mysteries of life and developing new therapeutic strategies to combat diseases.
[395] Regulation of gene expression - Wikipedia — Regulation of gene expression by a hormone receptor Diagram showing at which stages in the DNA-mRNA-protein pathway expression can be controlled Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. In multicellular organisms, gene regulation drives cellular differentiation and morphogenesis in the embryo, leading to the creation of different cell types that possess different gene expression profiles from the same genome sequence.
[396] Transcriptional Regulation: Molecules, Involved Mechanisms, and ... — In turn, these novel strategies provided a fuller understanding of how DNA sequence information, epigenetic modifications, and transcription machinery cooperate to regulate gene expression. They cover all subjects of transcriptional regulation, from cis-regulatory elements to transcription factors, chromatin regulators, and ncRNAs. Additionally, several transcriptome studies and computational analyses are also included in this issue. Likewise, to date, a lot of similar studies have led to a better comprehension of the pathogenetic mechanisms as well as the discovery of novel biomarkers and/or therapeutic targets for these human disorders, as cited in a review dissecting the role of Adiponectin as a link factor between adipose tissue and cancer . Numerous epigenetic mechanisms other than regulation by ncRNAs take place during RNA polymerase II-transcription and may be involved in human pathophysiology.
[397] Meta-Analysis of Gene Expression and Identification of Biological ... — Keywords: Alzheimer's disease, long non-coding RNA, microRNA, single nucleotide polymorphisms, network, meta-analysis. Citation: Su L, Chen S, Zheng C, Wei H and Song X (2019) Meta-Analysis of Gene Expression and Identification of Biological Regulatory Mechanisms in Alzheimer's Disease. Front. Neurosci. 13:633. doi: 10.3389/fnins.2019.00633