Somatic Mosaicism in Biology and Disease

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Hayato Ogawa ◽  
Keita Horitani ◽  
Yasuhiro Izumiya ◽  
Soichi Sano
Keyword(s):  
Genome Sequencing ◽  
Somatic Mutations ◽  
Somatic Mosaicism ◽  
Clinical Information ◽  
Annual Review ◽  
Clinical Implications ◽  
Publication Date ◽  
Sequencing Data ◽  
Sequencing Technology ◽  
The Individual

Contrary to earlier beliefs, every cell in the individual is genetically different due to somatic mutations. Consequently, tissues become a mixture of cells with distinct genomes, a phenomenon termed somatic mosaicism. Recent advances in genome sequencing technology have unveiled possible causes of mutations and how they shape the unique mutational landscape of the tissues. Moreover, the analysis of sequencing data in combination with clinical information has revealed the impacts of somatic mosaicism on disease processes. In this review, we discuss somatic mosaicism in various tissues and its clinical implications for human disease. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Cultivating Resilience During the COVID-19 Pandemic: A Socioecological Perspective

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Ning Zhang ◽  
Shujuan Yang ◽  
Peng Jia
Keyword(s):  
Cost Effective ◽  
Future Research ◽  
Annual Review ◽  
Publication Date ◽  
Physical And Mental Health ◽  
Pandemic Preparedness ◽  
Predicting Factors ◽  
Effective Interventions ◽  
Interdisciplinary Framework ◽  
The Individual

The coronavirus disease 2019 (COVID-19) pandemic poses wide-ranging impacts on the physical and mental health of people around the world, increasing attention from both researchers and practitioners on the topic of resilience. In this article, we review previous research on resilience from the past several decades, focusing on how to cultivate resilience during emerging situations such as the COVID-19 pandemic at the individual, organizational, community, and national levels from a socioecological perspective. Although previous research has greatly enriched our understanding of the conceptualization, predicting factors, processes, and consequences of resilience from a variety of disciplines and levels, future research is needed to gain a deeper and comprehensive understanding of resilience, including developing an integrative and interdisciplinary framework for cultivating resilience, developing an understanding of resilience from a life span perspective, and developing scalable and cost-effective interventions for enhancing resilience and improving pandemic preparedness. Expected final online publication date for the Annual Review of Psychology, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Unique K-mer sequences for validating cancer-related substitution, insertion and deletion mutations

2020 ◽  
Author(s):  
HoJoon Lee ◽  
Ahmed Shuaibi ◽  
John M. Bell ◽  
Dmitri S. Pavlichin ◽  
Hanlee P. Ji
Keyword(s):  
Genome Sequencing ◽  
Somatic Mutations ◽  
Variant Calling ◽  
Cancer Genome ◽  
Sequencing Data ◽  
Deletion Mutations ◽  
Insertion And Deletion ◽  
Cancer Genome Sequencing ◽  
Significant Difference ◽  
Model Tuning

ABSTRACTThe cancer genome sequencing has led to important discoveries such as identifying cancer gene. However, challenges remain in the analysis of cancer genome sequencing. One significant issue is that mutations identified by multiple variant callers are frequently discordant even when using the same genome sequencing data. For insertion and deletion mutations, oftentimes there is no agreement among different callers. Identifying somatic mutations involves read mapping and variant calling, a complicated process that uses many parameters and model tuning. To validate the identification of true mutations, we developed a method using k-mer sequences. First, we characterized the landscape of unique versus non-unique k-mers in the human genome. Second, we developed a software package, KmerVC, to validate the given somatic mutations from sequencing data. Our program validates the occurrence of a mutation based on statistically significant difference in frequency of k-mers with and without a mutation from matched normal and tumor sequences. Third, we tested our method on both simulated and cancer genome sequencing data. Counting k-mer involving mutations effectively validated true positive mutations including insertions and deletions across different individual samples in a reproducible manner. Thus, we demonstrated a straightforward approach for rapidly validating mutations from cancer genome sequencing data.

scholarly journals Challenging a bioinformatic tool’s ability to detect microbial contaminants usingin silicowhole genome sequencing data

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3729 ◽  
Author(s):  
Nathan D. Olson ◽  
Justin M. Zook ◽  
Jayne B. Morrow ◽  
Nancy J. Lin
Keyword(s):  
Binary Mixtures ◽  
Genome Sequencing ◽  
Pathogen Detection ◽  
A Priori ◽  
High Sensitivity ◽  
False Positives ◽  
Sequencing Data ◽  
Materials Used ◽  
The Individual ◽  
Genome Assemblies

High sensitivity methods such as next generation sequencing and polymerase chain reaction (PCR) are adversely impacted by organismal and DNA contaminants. Current methods for detecting contaminants in microbial materials (genomic DNA and cultures) are not sensitive enough and require either a known or culturable contaminant. Whole genome sequencing (WGS) is a promising approach for detecting contaminants due to its sensitivity and lack of need fora prioriassumptions about the contaminant. Prior to applying WGS, we must first understand its limitations for detecting contaminants and potential for false positives. Herein we demonstrate and characterize a WGS-based approach to detect organismal contaminants using an existing metagenomic taxonomic classification algorithm. Simulated WGS datasets from ten genera as individuals and binary mixtures of eight organisms at varying ratios were analyzed to evaluate the role of contaminant concentration and taxonomy on detection. For the individual genomes the false positive contaminants reported depended on the genus, withStaphylococcus,Escherichia, andShigellahaving the highest proportion of false positives. For nearly all binary mixtures the contaminant was detected in thein-silicodatasets at the equivalent of 1 in 1,000 cells, thoughF. tularensiswas not detected in any of the simulated contaminant mixtures andY. pestiswas only detected at the equivalent of one in 10 cells. Once a WGS method for detecting contaminants is characterized, it can be applied to evaluate microbial material purity, in efforts to ensure that contaminants are characterized in microbial materials used to validate pathogen detection assays, generate genome assemblies for database submission, and benchmark sequencing methods.

Revisiting Behavioral Integrity: Progress and New Directions After 20 Years

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Tony Simons ◽  
Hannes Leroy ◽  
Lisa Nishii
Keyword(s):  
Organizational Behavior ◽  
Future Research ◽  
Annual Review ◽  
Publication Date ◽  
Behavioral Integrity ◽  
Positive Behaviors ◽  
Positive Attitudes ◽  
Leadership Initiatives ◽  
And Performance ◽  
The Individual

Behavioral integrity (BI) describes the extent to which an observer believes that an actor's words tend to align with their actions. It considers whether the actor is seen as keeping promises and enacting the same values they espouse. Although the construct of BI was introduced in 1999 and developed more fully in 2002, it builds on the work of earlier scholars that discussed related notions of hypocrisy, credibility, and gaps between espousal and enactment. Since the 2002 paper, a growing literature has established the BI construct, largely but not exclusively in the leadership realm, as a critical antecedent to positive attitudes such as trust and commitment, positive behaviors such as turnover and performance, and as a moderator of the effectiveness of leadership initiatives. BI is by definition subjectively assessed, and perceptions of BI are susceptible to various forms of perceptual biases. A variety of factors appear to affect whether observers interpret a particular word-action alignment or gap as an indication of the actor's high or low BI. In this article, we examine and synthesize this literature and suggest directions for future research. We discuss the early history of BI research and then examine contemporary research at the individual, group, and organizational levels of analysis. We assess what we have learned and what methodological challenges and theoretical questions remain to be addressed. We hope in this way to stimulate further research on this consequential construct. Expected final online publication date for the Annual Review of Organizational Psychology and Organizational Behavior, Volume 9 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The tracrRNA in CRISPR Biology and Technologies

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Chunyu Liao ◽  
Chase L. Beisel
Keyword(s):  
Genetic Material ◽  
Immune Defense ◽  
Annual Review ◽  
Publication Date ◽  
Traditional Role ◽  
Guide Rnas ◽  
Technological Advances ◽  
Guide Sequence ◽  
The Individual ◽  
New Applications

CRISPR-Cas adaptive immune systems in bacteria and archaea utilize short CRISPR RNAs (crRNAs) to guide sequence-specific recognition and clearance of foreign genetic material. Multiple crRNAs are stored together in a compact format called a CRISPR array that is transcribed and processed into the individual crRNAs. While the exact processing mechanisms vary widely, some CRISPR-Cas systems, including those encoding the Cas9 nuclease, rely on a trans-activating crRNA (tracrRNA). The tracrRNA was discovered in 2011 and was quickly co-opted to create single-guide RNAs as core components of CRISPR-Cas9 technologies. Since then, further studies have uncovered processes extending beyond the traditional role of tracrRNA in crRNA biogenesis, revealed Cas nucleases besides Cas9 that are dependent on tracrRNAs, and established new applications based on tracrRNA engineering. In this review, we describe the biology of the tracrRNA and how its ongoing characterization has garnered new insights into prokaryotic immune defense and enabled key technological advances. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Causative Microbes in Host-Microbiome Interactions

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Graham J. Britton ◽  
Jeremiah J. Faith
Keyword(s):  
Immune System ◽  
Human Microbiome ◽  
Individual Species ◽  
Annual Review ◽  
Publication Date ◽  
Sequencing Technology ◽  
Specific Effects ◽  
Therapeutic Benefits ◽  
Experimental Approaches

Despite identification of numerous associations between microbiomes and diseases, the complexity of the human microbiome has hindered identification of individual species and strains that are causative in host phenotype or disease. Uncovering causative microbes is vital to fully understand disease processes and to harness the potential therapeutic benefits of microbiota manipulation. Developments in sequencing technology, animal models, and bacterial culturing have facilitated the discovery of specific microbes that impact the host and are beginning to advance the characterization of host-microbiome interaction mechanisms. We summarize the historical and contemporary experimental approaches taken to uncover microbes from the microbiota that affect host biology and describe examples of commensals that have specific effects on the immune system, inflammation, and metabolism. There is still much to learn, and we lay out challenges faced by the field and suggest potential remedies for common pitfalls encountered in the hunt for causative commensal microbes. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Comprehensive identification of somatic nucleotide variants in human brain tissue

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yifan Wang ◽  
◽  
Taejeong Bae ◽  
Jeremy Thorpe ◽  
Maxwell A. Sherman ◽  
...  
Keyword(s):  
Best Practices ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Somatic Mosaicism ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Single Individual ◽  
Sequencing Data ◽  
Specificity And Sensitivity ◽  
Neuropsychiatric Diseases

Abstract Background Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Results Here, the Brain Somatic Mosaicism Network conducts a coordinated, multi-institutional study to examine the ability of existing methods to detect simulated somatic single-nucleotide variants (SNVs) in DNA mixing experiments, generate multiple replicates of whole-genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual, devise strategies to discover somatic SNVs, and apply various approaches to validate somatic SNVs. These efforts lead to the identification of 43 bona fide somatic SNVs that range in variant allele fractions from ~ 0.005 to ~ 0.28. Guided by these results, we devise best practices for calling mosaic SNVs from 250× whole-genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrate that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees. Conclusions This study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.

scholarly journals Molecular Basis of Lysis–Lysogeny Decisions in Gram-Positive Phages

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Aisling Brady ◽  
Alonso Felipe-Ruiz ◽  
Francisca Gallego del Sol ◽  
Alberto Marina ◽  
Nuria Quiles-Puchalt ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Level ◽  
Temperate Phage ◽  
Lytic Cycle ◽  
Annual Review ◽  
Publication Date ◽  
Host Bacterium ◽  
Gram Positive ◽  
Susceptible Host ◽  
The Individual

Temperate bacteriophages (phages) are viruses of bacteria. Upon infection of a susceptible host, a temperate phage can establish either a lytic cycle that kills the host or a lysogenic cycle as a stable prophage. The life cycle pursued by an infecting temperate phage can have a significant impact not only on the individual host bacterium at the cellular level but also on bacterial communities and evolution in the ecosystem. Thus, understanding the decision processes of temperate phages is crucial. This review delves into the molecular mechanisms behind lysis–lysogeny decision-making in Gram-positive phages. We discuss a variety of molecular mechanisms and the genetic organization of these well-understood systems. By elucidating the strategies used by phages to make lysis–lysogeny decisions, we can improve our understanding of phage–host interactions, which is crucial for a variety of studies including bacterial evolution, community and ecosystem diversification, and phage therapeutics. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Brain Somatic Mutation in Aging and Alzheimer's Disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Michael B. Miller ◽  
Hannah C. Reed ◽  
Christopher A. Walsh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Human Genetics ◽  
Annual Review ◽  
Publication Date ◽  
Technological Advances ◽  
Human Neurons ◽  
The Brain

Somatic mutations arise postzygotically, producing genetic differences between cells in an organism. Well established as a driver of cancer, somatic mutations also exist in nonneoplastic cells, including in the brain. Technological advances in nucleic acid sequencing have enabled recent breakthroughs that illuminate the roles of somatic mutations in aging and degenerative diseases of the brain. Somatic mutations accumulate during aging in human neurons, a process termed genosenium. A number of recent studies have examined somatic mutations in Alzheimer's disease (AD), primarily from the perspective of genes causing familial AD. We have also gained new information on genome-wide mutations, providing insights into the cellular events driving somatic mutation and cellular dysfunction. This review highlights recent concepts, methods, and findings in the progress to understand the role of brain somatic mutation in aging and AD. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Comprehensive identification of somatic nucleotide variants in human brain tissue

2020 ◽  
Author(s):  
Yifan Wang ◽  
Taejeong Bae ◽  
Jeremy Thorpe ◽  
Maxwell A. Sherman ◽  
Attila G. Jones ◽  
...  
Keyword(s):  
Best Practices ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Somatic Mosaicism ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Single Individual ◽  
Sequencing Data ◽  
Specificity And Sensitivity ◽  
Neuropsychiatric Diseases

AbstractPost-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Here, the Brain Somatic Mosaicism Network conducted a coordinated, multi-institutional study to: (i) examine the ability of existing methods to detect simulated somatic single nucleotide variants (SNVs) in DNA mixing experiments; (ii) generate multiple replicates of whole genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual; (iii) devise strategies to discover somatic SNVs; and (iv) apply various approaches to validate somatic SNVs. These efforts led to the identification of 43 bona fide somatic SNVs that ranged in variant allele fractions from ~0.005 to ~0.28. Guided by these results, we devised best practices for calling mosaic SNVs from 250X whole genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrated that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees. Thus, this study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.

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