Human Genome Project Research Articles

Are non-protein coding RNAs junk or treasure?: An attempt to explain and reconcile opposing viewpoints of whether the human genome is mostly transcribed into non-functional or functional RNAs.

The human genome project's lasting legacies are the emerging insights into human physiology and disease, and the ascendance of biology as the dominant science of the 21st century. Sequencing revealed that >90% of the human genome is not coding for proteins, as originally thought, but rather is overwhelmingly transcribed into non-protein coding, or non-coding, RNAs (ncRNAs). This discovery initially led to the hypothesis that most genomic DNA is "junk", a term still championed by some geneticists and evolutionary biologists. In contrast, molecular biologists and biochemists studying the vast number of transcripts produced from most of this genome "junk" often surmise that these ncRNAs have biological significance. What gives? This essay contrasts the two opposing, extant viewpoints, aiming to explain their bases, which arise from distinct reference frames of the underlying scientific disciplines. Finally, it aims to reconcile these divergent mindsets in hopes of stimulating synergy between scientific fields.

Precision Population Cancer Medicine in Cancer of the Uterine Cervix: A Potential Roadmap to Eradicate Cervical Cancer.

With the success of the Human Genome Project, the era of genomic medicine (GM) was born. Later on, as GM made progress, there was a feeling of exhilaration that GM could help resolve many disease processes. It also led to the conviction that personalized medicine was possible, and a relatively synonymous word, precision medicine (PM), was coined. However, the influence of environmental factors and social determinants of diseases was only partially given their due importance in the definition of PM, although more recently, this has been recognized. With the rapid advances in GM, big data, data mining, wearable devices for health monitoring, telemedicine, etc., PM can be more easily extended to population-level health care in disease management, prevention, early screening, and so on.and the term precision population medicine (PPM) more aptly describes it. PPM's potential in cancer care was posited earlier,and the current authors planned a series of cancer disease-specific follow-up articles. These papers are mainly aimed at helping emerging students in health sciences (medicine, pharmacy, nursing, dentistry, public health, population health), healthcare management (health-focused business administration, nonprofit administration, public institutional administration, etc.), and policy-making (e.g., political science), although not exclusively. This first disease-specific report focuses on the cancer of the uterine cervix (CC). It describes how recent breakthroughs can be leveraged as force multipliers to improve outcomes in CC - by improving early detection, better screening for CC, potential GM-based interventions during the stage of persistent Human papillomavirus (HPV) infection and treatment interventions - especially among the disadvantaged and resource-scarce populations. This work is a tiny step in our attempts to improve outcomes in CC and ultimately eradicate CC from the face of the earth.

The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT) toward a Human Exposome Project.

The Human Exposome Project aims to revolutionize our understanding of how environmental exposures affect human health by systematically cataloging and analyzing the myriad exposures individuals encounter throughout their lives. This initiative draws a parallel with the Human Genome Project, expanding the focus from genetic factors to the dynamic and complex nature of environ-mental interactions. The project leverages advanced methodologies such as omics technologies, biomonitoring, microphysiological systems (MPS), and artificial intelligence (AI), forming the foun-dation of exposome intelligence (EI) to integrate and interpret vast datasets. Key objectives include identifying exposure-disease links, prioritizing hazardous chemicals, enhancing public health and regulatory policies, and reducing reliance on animal testing. The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT), spearheaded by the Center for Alternatives to Animal Testing (CAAT), is a new element in this endeavor, driving the creation of a public-private part-nership toward a Human Exposome Project with a stakeholder forum in 2025. Establishing robust infrastructure, fostering interdisciplinary collaborations, and ensuring quality assurance through sys-tematic reviews and evidence-based frameworks are crucial for the project's success. The expected outcomes promise transformative advancements in precision public health, disease prevention, and a more ethical approach to toxicology. This paper outlines the strategic imperatives, challenges, and opportunities that lie ahead, calling on stakeholders to support and participate in this landmark initiative for a healthier, more sustainable future.

BIG to CNCB: An Exploratory Journey from Genomics to Bioinformation

The Beijing Institute of Genomics (BIG) of the Chinese Academy of Sciences, as the leading Institute in Genomics, has walked through 20 year’s journey since being founded in November 2003. From participating in the Human Genome Project (HGP) in completing the “1% task” to independently accomplishing the super-hybrid rice genome and other several national and international genome projects, BIG has made tremendous contributions in genomics research and development in China. In 2024, bearing great ambition and responsibility, BIG is transformed to the China National Center for Bioinformation (CNCB), aiming to become a global hub in bioinformatics big data services, innovation, and entrepreneurship. With the completion of its new infrastructure in 2027, CNCB is looking into a brighter future.

The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT) toward a Human Exposome Project.

The Human Exposome Project aims to revolutionize our understanding of how environmental exposures affect human health by systematically cataloging and analyzing the myriad exposures individuals encounter throughout their lives. This initiative draws a parallel with the Human Genome Project, expanding the focus from genetic factors to the dynamic and complex nature of environ-mental interactions. The project leverages advanced methodologies such as omics technologies, biomonitoring, microphysiological systems (MPS), and artificial intelligence (AI), forming the foun-dation of exposome intelligence (EI) to integrate and interpret vast datasets. Key objectives include identifying exposure-disease links, prioritizing hazardous chemicals, enhancing public health and regulatory policies, and reducing reliance on animal testing. The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT), spearheaded by the Center for Alternatives to Animal Testing (CAAT), is a new element in this endeavor, driving the creation of a public-private part-nership toward a Human Exposome Project with a stakeholder forum in 2025. Establishing robust infrastructure, fostering interdisciplinary collaborations, and ensuring quality assurance through sys-tematic reviews and evidence-based frameworks are crucial for the project's success. The expected outcomes promise transformative advancements in precision public health, disease prevention, and a more ethical approach to toxicology. This paper outlines the strategic imperatives, challenges, and opportunities that lie ahead, calling on stakeholders to support and participate in this landmark initiative for a healthier, more sustainable future.

Neutrosophic Sets in Investigating the Right to Genetic Information: A Study using Fuzzy Cognitive Maps and D-OWA

This article provides a comprehensive view of the evolution and ethical implications of genetics, from its historical origins to modern advancements like the Human Genome Project. It emphasizes the importance of genetic information in disease prediction and understanding human diversity while highlighting the need to address associated ethical and privacy issues. It introduces Fuzzy Cognitive Maps (FCM) and the Dependent OWA (D-OWA) aggregation operator as innovative tools for analyzing the complex landscape of the Right to Genetic Information (RGI) in an international context, identifying key factors such as legal frameworks, technological advancements, access to health, culture, ethics, and commercial interests. The research reveals that while legal framework and technology are predominant, other factors also play significant roles in managing RGI. The application of D-OWA provides additional insights, confirming that conventional centrality assessments adequately reflect the priorities and influence of factors in RGI. It concludes by underlining the need for specific strategies to address these challenges, such as strengthening the legal framework, promoting ethics in genetics, improving public education, and respecting cultural diversity, to protect individual rights while leveraging the benefits of genetics for society.

'Almost nothing is firmly established': A History of Heredity and Genetics in Mental Health Science.

For more than a century, scientists have tried to find the key to causation of mental ill health in heredity and genetics. The difficulty of finding clear and actionable answers in our genes has not stopped them looking. This history offers important context to understanding mental health science today. This article explores the main themes in research on genetics and inheritance in psychiatry from the second half of the nineteenth century to the present day, to address the question: what is the history of genetics as a causative explanation in mental health science? We take a critical historical approach to the literature, interrogating primary and secondary material for the light it brings to the research question, while considering the social and historical context. We begin with the statistics gathered in asylums and used to 'prove' the importance of heredity in mental ill health. We then move through early twentieth century Mendelian models of mental inheritance, the eugenics movement, the influence of social psychiatry, new classifications and techniques of the postwar era, the Human Genome Project and Genome Wide Association Studies (GWAS) and epigenetics. Setting these themes in historical context shows that this research was often popular because of wider social, political and cultural issues, which impacted the views of scientists just as they did those of policymakers, journalists and the general public. We argue that attempting to unpick this complex history is essential to the modern ethics of mental health and genetics, as well as helping to focus our efforts to better understand causation in mental ill-health.For a succinct timeline of the history of psychiatric genetics, alongside the history of other proposed causes for mental ill-health, visit: https://historyofcauses.co.uk/.

A Quantitative Approach in Identifying Natural Selection Signals on Biallelic Single Nucleotide Polymorphisms of BRCA1 Gene in Diverse Populations

Population-specific studies reveal that cancer-related mechanisms of BRCA1 gene mutations may vary by ethnicity. The wealth of public genomic data provides insight into the functional roles of BRCA1 in diverse populations. In this study, we performed population differentiation analysis on biallelic SNPs located in the BRCA1 region using variant-calling data from the 1000 Human Genome Project. First, we conducted an Analysis of Molecular Variance (AMOVA) in global populations to infer a differentiation of BRCA1 gene in three population-related hierarchical levels. An FST-based approach was also conducted for each defined locus in the gene. Moreover, the signals of the natural selection in BRCA1 gene were computed using integrated Haplotype Score (iHS) per locus. The results demonstrated that BRCA1 gene differentiation can be attributed to the continental difference, for example, the genetic difference between Asian and African superpopulations accounts for 25% of the total variance. Imposing the iHS computation, we found that only two East Asian populations that underwent a positive selection, in which only benign variants were observed. In addition, those putative variants are only found in the non-coding regions: intron and 3’ UTR. Our study is expected to ignite research interest in cancer-related genes for underrepresented populations.

Did the human genome project affect research on Schizophrenia?

The Human Genome Project was undertaken primarily to discover genetic causes and better treatments for human diseases. Schizophrenia was targeted since three of the project`s principal architects had a personal interest and also because, based on family, adoption, and twin studies, schizophrenia was widely believed to be a genetic disorder. Extensive studies using linkage analysis, candidate genes, genome wide association studies [GWAS], copy number variants, exome sequencing and other approaches have failed to identify causal genes. Instead, they identified almost 300 single nucleotide polymorphisms [SNPs] associated with altered risks of developing schizophrenia as well as some rare variants associated with increased risk in a small number of individuals. Risk genes play a role in the clinical expression of most diseases but do not cause the disease in the absence of other factors. Increasingly, observers question whether schizophrenia is strictly a genetic disorder. Beginning in 1996 NIMH began shifting its research resources from clinical studies to basic research based on the promise of the Human Genome Project. Consequently, three decades later NIMH's genetics investment has yielded almost nothing clinically useful for individuals currently affected. It is time to review NIMH`s schizophrenia research portfolio.

SENNET CONSORTIUM: OPPORTUNITIES AND CHALLENGES

Abstract The Cellular Senescence Network (SenNet) Program was established in 2021 by the NIH Director’s Office Common Fund with the goal of comprehensively identifying and characterizing senescent cells across human lifespan in numerous organs. Mapping senescent cells in mice was added in 2022 to leverage genetic and pharmacologic approaches to drive, report, and ablate senescence in vivo. Senescent cells are implicated in driving most if not all age-related chronic diseases as well as accelerated aging caused by chronic diseases and their treatments (e.g., cancer chemotherapy). Furthermore, therapeutics specifically targeting senescent cells (senotherapeutics) have been developed and are currently being tested in clinical trials for multiple disease and geriatric endpoints. Thus, identifying and characterizing senescent cells throughout human aging and disease states has the potential to significantly impact human health. The SenNet Consortium is a highly collaborative network of scientists across the globe jointly benchmarking tools, technologies, and data analytic approaches, and aligning their activities with other NIH Common Fund initiatives, such as HuBMAP. While mapping senescent cells holds great biomedical promise, there are challenges such as the absence of specific biomarker to identify senescent cells, the appearance of senescence under physiological and pathological conditions, and little knowledge of what drives senescence in vivo. Analogous to the Human Genome Project, to achieve SenNet goals, innovative tools and technologies for single cell and spatial tissue analysis must be developed. Products of SenNet, in addition these new approaches, will include common nomenclature to define senescent cells, novel biomarkers of senescent cells, and publicly accessible databases and 4D atlases of senescent cells in 18 human and murine organs that enables 4D visualization.

Omics and AI in precision medicine: Maintaining socio-technical imaginaries by transforming technological assemblages

We understand precision medicine as a socio-technical imaginary according to Jasanoff. After briefly outlining how the imaginary of precision medicine emerged from the Human Genome Project and spread across national contexts, we raise the question of why the imaginary and the expectations and promises associated with it persist despite regular disappointment among practitioners about the failure of personalized healthcare. We argue that short-term technological hypes enable stakeholders to renew and maintain the promises of precision medicine. In our view, these hypes are around transformations of a technological assemblage. We discuss this in detail for omics and AI technologies and evaluate the recent transformations in light of the long-term imaginary of precision medicine.

A Global Survey of Precision Medicine in Emergency General Surgery

Abstract Background Since first sequencing the human genome, precision medicine has become a modern-day reality. However, translation to all areas of medicine has not been equal. This study aimed to provide a ‘status update’ of precision medicine in EGS to guide future priority setting. Methodology An observational study was conducted utilising two curated global on-line databases: 1. Pubmed publications from 2001 & 2. Clinical trials registered on ClinicalTrials.gov. The top 10 presenting conditions in EGS, Oncology, and Acute Medicine were identified from literature review. Publications/trials in these areas were identified using associated keywords: precision, personalised, genomics, genome-wide association studies, exome studies, epigenetics, transcriptomics, proteomics, metabolomics, microbiomics, and pharmacogenomics. Duplicated publications/trials were removed prior to final analysis and only active, recruiting or completed trials were included. Temporal trends were compared and annual growth rates were calculated. Results There were 209,423 EGS publications, 1807 (0.9%) being precision-focused. Oncology had 1,137,396 publications, with 127,556 precision-focused (11.2%), and Acute Medicine had 1,647,046 publications, with 80,240 (4.9%) precision-focused. The rate of rise of annual publications since 2001 (human genome project publication) was significantly (p<0.05) lower for EGS (x2.9) versus oncology (x3.5) and medicine (x6.0). Only 7 precision-focused clinical trials were identified for EGS compared to 96 for Oncology and 39 for Medicine. x10 fewer precision-focused EGS publications and trials exist over 20 years, compared to covid-19 over 2 years. Conclusion Research and implementation of precision medicine in EGS remains inadequate. Increased investment and improved global implementation are warranted to address the widening gap in translation.

Preimplantation Genetic Testing for Single Gene Conditions and Aneuploidy

It is now over 30 years since the first pregnancies and live births following IVF, embryo biopsy and preimplantation genetic testing (PGT) were reported in 1990. Since then, methods for genetic analysis at the single-cell level have evolved alongside the rapid advances in human genetics and sequencing of the human genome. With the development of methods for whole genome amplification, such as multiple displacement amplification (MDA), genome-wide analysis is now possible. This has led to the development of microarray or next generation sequencing (NGS) based methods for genome-wide haplotyping of parental chromosomes in embryo samples and enabled universal linkage-based testing for monogenic diseases combined with molecular cytogenetic analysis of chromosome abnormalities. These comprehensive methods have also recently been exploited to calculate polygenic risk scores for common multifactorial conditions, such as diabetes, cardiovascular disease, and cancer. Although controversial, polygenic risk scoring may have a role for reducing residual risk of breast cancer, for example, in combination with PGT for pathogenic variants. Finally, there is now evidence that cell-free DNA in spent culture medium at the blastocyst stage may originate from nuclear DNA shedding from the trophectoderm. In the future, therefore, it may be possible to use this cell-free DNA for genome-wide analysis and comprehensive PGT to avoid embryo biopsy.

Genomics education for advance practice nurses: Staying cutting edge.

As we celebrate the 20th anniversary of sequencing of the human genome and the rapid integration of genetics in health care, we pause to reflect on the status of genomic competency in nursing. The literature provides evidence that nurses do not feel prepared or confident in genomics. Genomic education for nurses and other health care professionals can support access and equity in the integration of genomics into practice. Resources are provided to support genomic education and clinical support.

A substituição nua: o apoio de geneticistas e biotecnólogos à eugenia da Segunda Guerra Mundial ao Projeto Genoma Humano

ABSTRACT Using a combination of archival and secondary sources, this article argues that scientists and bioethicists after the Second World War advocated a wide variety of eugenic practices and strongly supported the development of eugenics, strengthened by advances in medicine, human genetics, and population genetics. I detail extensive research in both the Curt Stern and the American Eugenics Society Papers (American Philosophical Society in Philadelphia), uncovering novel defenses of eugenics and its integration in sciences after the Second World War by key figures such as Curt Stern and Theodosius Dobzhansky. Moreover, I relate to Richard Lewontin’s participation in a Princeton conference sponsored by the American Eugenics Society in 1965. This article is also the first to not only describe geneticists’ defense and development of eugenic ideas but also details bioethicists’ defense of this inhumane and unscientific ideology until the dawn of the Human Genome Project in the late 1980s.

A conceptual analysis of public opinion regarding genome research in Japan

In the 20 years since the completion of the Human Genome Project, the gap between scientific development and public understanding of genome research has been widening. While genome research has been increasingly utilized for social and clinical purposes in a multifaceted manner, this has resulted in an increase in the potential risks associated with genomic data. In this context, our study aims to consider the nature of public perceptions of genome research, primarily by using as a case study the results of previous public surveys relevant to donations for social benefits in Japan. We explored certain types of awareness, attitude, and intention (A-A-I) in such surveys and discussed the resultant key findings through the cultural transmission framework. Reframing the public’s response toward genome research based on A-A-I analysis and behavioral science may contribute to developing more systematic communication approaches with the public. With a view to establishing such approaches, our perspective suggests some new insights to discuss the science–society gap in genome research internationally.

Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis

Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC.

Comprehensive genomic profiling for oncological advancements by precision medicine.

Considerable advancements in next generation sequencing (NGS) techniques have sparked the use of comprehensive genomic profiling (CGP) as a guiding tool for precision-centered oncological treatments. The past two decades have seen the completion of the human genome project, and the consequential invention of NGS. High-throughput sequencing technologies support the discovery and commonplace use of individualized cancer treatments, specifically immune-centered checkpoint inhibitor therapies, and oncogene and tumor suppressor gene targeted therapies. Nevertheless, CGP is not commonly used in all clinical settings. This review investigates the clinically relevant applications of CGP. Studies published between the years 2000-2023 have shown substantial evidence of the benefits of integrating CGP into routine care practice, while also making important comparisons to current-standard oncological treatment strategies. Findings of a comprehensive genomic profile includes predictive, prognostic, and diagnostic biomarkers, together with somatic mutation identification which can indicate the efficacy of immunotherapies and molecularly guided therapies. This review highlights the importance of CGP in identifying driver mutations in tumors that subsequently can be effectively targeted with molecular therapeutics and lead to drug discovery, allowing for increased precision in treating tumors selectively based on their specific genetic mutations, thereby improving patient outcomes.

The use of gene expression datasets in feature selection research: 20 years of inherent bias?

AbstractFeature selection algorithms are frequently employed in preprocessing machine learning pipelines applied to biological data to identify relevant features. The use of feature selection in gene expression studies began at the end of the 1990s with the analysis of human cancer microarray datasets. Since then, gene expression technology has been perfected, the Human Genome Project has been completed, new microarray platforms have been created and discontinued, and RNA‐seq has gradually replaced microarrays. However, most feature selection methods in the last two decades were designed, evaluated, and validated on the same datasets from the microarray technology's infancy. In this review of over 1200 publications regarding feature selection and gene expression, published between 2010 and 2020, we found that 57% of the publications used at least one outdated dataset, 23% used only outdated data, and 32% did not cite data sources. Other issues include referencing databases that are no longer available, the slow adoption of RNA‐seq datasets, and bias toward human cancer data, even for methods designed for a broader scope. In the most popular datasets, some being 23 years old, mislabeled samples, experimental biases, distribution shifts, and the absence of classification challenges are common. These problems are more predominant in publications with computer science backgrounds compared to publications from biology and can lead to inaccurate and misleading biological results.This article is categorized under: Algorithmic Development > Biological Data Mining Technologies > Machine Learning

GENETIC TESTING IN THE ORTHOPAEDIC CLINIC

Medical Genetics is a transversal discipline with the potential to impact on every specialty and subspecialty in medicine and the allied health sciences. The completion of the human genome project resulted in technical advancements in genomics, genomic testing and our understanding of genetic disorders in general. These advancements have greatly enhanced our understanding of the role of genetics in Orthopaedic practice, with respect to both monogenic and complex disorders. Tygerberg Hospital is currently the only state hospital in South Africa to support genetic testing in the form of gene panels as part of routine care. This is complemented by more comprehensive research testing in the form of exome and genome sequencing as part of the Undiagnosed Disease Programme.We audit the genetic and genomic testing done on patients referred from the Orthopaedic clinic over a period of 3 years (2020–2022) and review diagnostic rates and interesting results.The largest group of patients referred (n=50) had a clinical diagnosis of osteogenesis imperfecta (OI). A 100% diagnostic yield was achieved for these patients with the identification of recurring variants (FKBP10, COL1A2). Further families (n=20) with much rarer conditions are presented with important implications on the orthopaedic and medical management, prognosis, and genetic counselling for the families.We highlight the impact of genomic testing in the Orthopaedic clinic. Management changes and precision orthopaedic intervention were only possible due to a genetic diagnosis. We motivate for increased access to testing, especially for younger patients presenting with complex orthopaedic phenotypes.