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"Snyder, Michael"
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Systematic identification of silencers in human cells
The majority of the human genome does not encode proteins. Many of these noncoding regions contain important regulatory sequences that control gene expression. To date, most studies have focused on activators such as enhancers, but regions that repress gene expression—silencers—have not been systematically studied. We have developed a system that identifies silencer regions in a genome-wide fashion on the basis of silencer-mediated transcriptional repression of caspase 9. We found that silencers are widely distributed and may function in a tissue-specific fashion. These silencers harbor unique epigenetic signatures and are associated with specific transcription factors. Silencers also act at multiple genes, and at the level of chromosomal domains and long-range interactions. Deletion of silencer regions linked to the drug transporter genes
ABCC2
and
ABCG2
caused chemo-resistance. Overall, our study demonstrates that tissue-specific silencing is widespread throughout the human genome and probably contributes substantially to the regulation of gene expression and human biology.
A genome-wide screen identifies silencer regions in human cells. Deletion of silencers linked to the transporter genes
ABCC2
and
ABCG2
causes their up-regulation and chemo-resistance.
Journal Article
الجينوميات والطب الشخصي : ما يحتاج الجميع إلى معرفته
إن الجينوميات في يومنا هذا، وهي جزء من حركة أكبر تجاه الطب الشخصي، متأهبة لإحداث ثورة في الرعاية الصحية وقد أدخلت بالفعل عناصر من الجينوميات على نطاق واسع من ذلك الفحوص المتقصية للأمراض قبل الولادة وعلاجات السرطان المستهدفة وبمزيد من الاختراعات وشيكة الوصول إلى أسرة المرضى صار أمل الثورة الجينومية لا حدود له ونظرا لما يواجه المستهلكين من الاختيارات الإضافية والقرارات الأكثر تعقيدا فيما يتعلق بصحتهم، يوضح سنايدر هذا الموضوع الذي قد يختلق أحيانا فيجعله نثرا واضحا عمليا.
Book
Integrative omics for health and disease
Advances in omics technologies -- such as genomics, transcriptomics, proteomics and metabolomics -- have begun to enable personalized medicine at an extraordinarily detailed molecular level. Individually, these technologies have contributed medical advances that have begun to enter clinical practice. However, each technology individually cannot capture the entire biological complexity of most human diseases. Integration of multiple technologies has emerged as an approach to provide a more comprehensive view of biology and disease. In this Review, we discuss the potential for combining diverse types of data and the utility of this approach in human health and disease. We provide examples of data integration to understand, diagnose and inform treatment of diseases, including rare and common diseases as well as cancer and transplant biology. Finally, we discuss technical and other challenges to clinical implementation of integrative omics.
Journal Article
Action Comics #1000
\"Action Comics #1 gave birth to America's greatest superhero, Superman. Now celebrate 1,000 issues of Action Comics with this collector's item hardcover, including an all-star lineup of writers and artists such as Brian Michael Bendis, Geoff Johns, Tom King, Brad Meltzer, Scott Snyder, Jim Lee, John Cassaday, Olivier Coipel, and an unpublished story from Marv Wolfman and ... Man of Steel artist Curt Swan, plus more\"-- Provided by publisher.
Book
Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information
A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.
Journal Article
Nonlinear dynamics of multi-omics profiles during human aging
Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes.
Understanding the molecular changes underlying aging is important for developing biomarkers and healthy aging interventions. In this study, the authors used comprehensive multi-omics data to reveal nonlinear molecular profiles across chronological ages, highlighting two substantial variations observed around ages 40 and 60, which are linked to increased disease risks.
Journal Article
The Integrative Human Microbiome Project
The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host–microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.
Over ten years, the Human Microbiome Project has provided resources for studying the microbiome and its relationship to disease; this Perspective summarizes the key achievements and findings of the project and its relationship to the broader field.
Journal Article
RNA-Seq: a revolutionary tool for transcriptomics
The development of high-throughput DNA sequencing methods provides a new method for mapping and quantifying transcriptomes — RNA sequencing (RNA-Seq). This article explains how RNA-Seq works, the challenges it faces and how it is changing our view of eukaryotic transcriptomes.
RNA-Seq is a recently developed approach to transcriptome profiling that uses deep-sequencing technologies. Studies using this method have already altered our view of the extent and complexity of eukaryotic transcriptomes. RNA-Seq also provides a far more precise measurement of levels of transcripts and their isoforms than other methods. This article describes the RNA-Seq approach, the challenges associated with its application, and the advances made so far in characterizing several eukaryote transcriptomes.
Journal Article
High‐throughput sequencing for biology and medicine
Advances in genome sequencing have progressed at a rapid pace, with increased throughput accompanied by plunging costs. But these advances go far beyond faster and cheaper. High‐throughput sequencing technologies are now routinely being applied to a wide range of important topics in biology and medicine, often allowing researchers to address important biological questions that were not possible before. In this review, we discuss these innovative new approaches—including ever finer analyses of transcriptome dynamics, genome structure and genomic variation—and provide an overview of the new insights into complex biological systems catalyzed by these technologies. We also assess the impact of genotyping, genome sequencing and personal omics profiling on medical applications, including diagnosis and disease monitoring. Finally, we review recent developments in single‐cell sequencing, and conclude with a discussion of possible future advances and obstacles for sequencing in biology and health.
Genome sequencing technologies have advanced rapidly, dramatically decreasing cost and increasing throughput. But beyond faster and cheaper, these advances have also stimulated the development of innovative new experimental approaches, and are opening new doors in human medicine and health.
Journal Article