Nature Reviews Genetics最新文献_第3页

Revealing gene function with statistical inference at single-cell resolution 以单细胞分辨率的统计推断揭示基因功能

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-07-01 DOI: 10.1038/s41576-024-00750-w

Cole Trapnell

{"title":"Revealing gene function with statistical inference at single-cell resolution","authors":"Cole Trapnell","doi":"10.1038/s41576-024-00750-w","DOIUrl":"10.1038/s41576-024-00750-w","url":null,"abstract":"Single-cell and spatial molecular profiling assays have shown large gains in sensitivity, resolution and throughput. Applying these technologies to specimens from human and model organisms promises to comprehensively catalogue cell types, reveal their lineage origins in development and discern their contributions to disease pathogenesis. Moreover, rapidly dropping costs have made well-controlled perturbation experiments and cohort studies widely accessible, illuminating mechanisms that give rise to phenotypes at the scale of the cell, the tissue and the whole organism. Interpreting the coming flood of single-cell data, much of which will be spatially resolved, will place a tremendous burden on existing computational pipelines. However, statistical concepts, models, tools and algorithms can be repurposed to solve problems now arising in genetic and molecular biology studies of development and disease. Here, I review how the questions that recent technological innovations promise to answer can be addressed by the major classes of statistical tools. Single-cell, spatial and multi-omic profiling technologies generate large-scale data that reveal the output of genome-scale experiments across diverse cells, tissues and organisms. Cole Trapnell reviews the underlying core statistical challenges that need to be tackled to harness the power of these technologies and advance our understanding of gene function in health and disease.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 9","pages":"623-638"},"PeriodicalIF":39.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Charting the evolutionary history of malaria 描绘疟疾的进化史

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-26 DOI: 10.1038/s41576-024-00756-4

Linda Koch

引用次数: 0

Methods and applications of genome-wide profiling of DNA damage and rare mutations DNA 损伤和罕见突变的全基因组图谱分析方法和应用

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-25 DOI: 10.1038/s41576-024-00748-4

Gerd P. Pfeifer, Seung-Gi Jin

{"title":"Methods and applications of genome-wide profiling of DNA damage and rare mutations","authors":"Gerd P. Pfeifer, Seung-Gi Jin","doi":"10.1038/s41576-024-00748-4","DOIUrl":"10.1038/s41576-024-00748-4","url":null,"abstract":"DNA damage is a threat to genome integrity and can be a cause of many human diseases, owing to either changes in the chemical structure of DNA or conversion of the damage into a mutation, that is, a permanent change in DNA sequence. Determining the exact positions of DNA damage and ensuing mutations in the genome are important for identifying mechanisms of disease aetiology when characteristic mutations are prevalent and probably causative in a particular disease. However, this approach is challenging particularly when levels of DNA damage are low, for example, as a result of chronic exposure to environmental agents or certain endogenous processes, such as the generation of reactive oxygen species. Over the past few years, a comprehensive toolbox of genome-wide methods has been developed for the detection of DNA damage and rare mutations at single-nucleotide resolution in mammalian cells. Here, we review and compare these methods, describe their current applications and discuss future research questions that can now be addressed. In this Review, Pfeifer and Jin discuss currently available methods for genome-wide mapping of DNA damage and rare mutations and illustrate how these technologies are being used to study mechanisms of mutagenesis linked to the aetiology of human diseases.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 12","pages":"846-863"},"PeriodicalIF":39.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sequencing-based analysis of microbiomes 基于测序的微生物组分析

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-25 DOI: 10.1038/s41576-024-00746-6

Yishay Pinto, Ami S. Bhatt

引用次数: 0

A digital marker for coronary artery disease 冠状动脉疾病的数字标记

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-24 DOI: 10.1038/s41576-024-00755-5

Linda Koch

引用次数: 0

Tandem repeats in the long-read sequencing era 长读数测序时代的串联重复序列

IF 42.7 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-19 DOI: 10.1038/s41576-024-00751-9

引用次数: 0

How germ granules promote germ cell fate 生殖颗粒如何促进生殖细胞的命运

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-18 DOI: 10.1038/s41576-024-00744-8

Melissa C. Pamula, Ruth Lehmann

{"title":"How germ granules promote germ cell fate","authors":"Melissa C. Pamula, Ruth Lehmann","doi":"10.1038/s41576-024-00744-8","DOIUrl":"10.1038/s41576-024-00744-8","url":null,"abstract":"Germ cells are the only cells in the body capable of giving rise to a new organism, and this totipotency hinges on their ability to assemble membraneless germ granules. These specialized RNA and protein complexes are hallmarks of germ cells throughout their life cycle: as embryonic germ granules in late oocytes and zygotes, Balbiani bodies in immature oocytes, and nuage in maturing gametes. Decades of developmental, genetic and biochemical studies have identified protein and RNA constituents unique to germ granules and have implicated these in germ cell identity, genome integrity and gamete differentiation. Now, emerging research is defining germ granules as biomolecular condensates that achieve high molecular concentrations by phase separation, and it is assigning distinct roles to germ granules during different stages of germline development. This organization of the germ cell cytoplasm into cellular subcompartments seems to be critical not only for the flawless continuity through the germline life cycle within the developing organism but also for the success of the next generation. In this Review, Pamula and Lehmann describe how distinct membraneless germ granules organize the germ cell cytoplasm at different stages of the germline life cycle to determine germ cell identity, maintain genome integrity and regulate gamete differentiation.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 11","pages":"803-821"},"PeriodicalIF":39.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BRCA1 and friends 30 years on 30 年后的 BRCA1 和朋友们

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-17 DOI: 10.1038/s41576-024-00754-6

William D. Foulkes

引用次数: 0

DNA packaging by molecular motors: from bacteriophage to human chromosomes 分子马达的 DNA 包装：从噬菌体到人类染色体

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-17 DOI: 10.1038/s41576-024-00740-y

Bram Prevo, William C. Earnshaw

{"title":"DNA packaging by molecular motors: from bacteriophage to human chromosomes","authors":"Bram Prevo, William C. Earnshaw","doi":"10.1038/s41576-024-00740-y","DOIUrl":"10.1038/s41576-024-00740-y","url":null,"abstract":"Dense packaging of genomic DNA is crucial for organismal survival, as DNA length always far exceeds the dimensions of the cells that contain it. Organisms, therefore, use sophisticated machineries to package their genomes. These systems range across kingdoms from a single ultra-powerful rotary motor that spools the DNA into a bacteriophage head, to hundreds of thousands of relatively weak molecular motors that coordinate the compaction of mitotic chromosomes in eukaryotic cells. Recent technological advances, such as DNA proximity-based sequencing approaches, polymer modelling and in vitro reconstitution of DNA loop extrusion, have shed light on the biological mechanisms driving DNA organization in different systems. Here, we discuss DNA packaging in bacteriophage, bacteria and eukaryotic cells, which, despite their extreme variation in size, structure and genomic content, all rely on the action of molecular motors to package their genomes. In this Review, the authors summarize DNA packaging in bacteriophage, bacteria and eukaryotic cells. They describe the difficulties each system faces when packaging its DNA, outline the molecular motor components involved, and provide insights from new studies that reveal how DNA organization is achieved.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 11","pages":"785-802"},"PeriodicalIF":39.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-generation data filtering in the genomics era 基因组时代的新一代数据过滤

IF 39.1 1区生物学

Nature Reviews Genetics Pub Date : 2024-06-14 DOI: 10.1038/s41576-024-00738-6

William Hemstrom, Jared A. Grummer, Gordon Luikart, Mark R. Christie

{"title":"Next-generation data filtering in the genomics era","authors":"William Hemstrom, Jared A. Grummer, Gordon Luikart, Mark R. Christie","doi":"10.1038/s41576-024-00738-6","DOIUrl":"10.1038/s41576-024-00738-6","url":null,"abstract":"Genomic data are ubiquitous across disciplines, from agriculture to biodiversity, ecology, evolution and human health. However, these datasets often contain noise or errors and are missing information that can affect the accuracy and reliability of subsequent computational analyses and conclusions. A key step in genomic data analysis is filtering — removing sequencing bases, reads, genetic variants and/or individuals from a dataset — to improve data quality for downstream analyses. Researchers are confronted with a multitude of choices when filtering genomic data; they must choose which filters to apply and select appropriate thresholds. To help usher in the next generation of genomic data filtering, we review and suggest best practices to improve the implementation, reproducibility and reporting standards for filter types and thresholds commonly applied to genomic datasets. We focus mainly on filters for minor allele frequency, missing data per individual or per locus, linkage disequilibrium and Hardy–Weinberg deviations. Using simulated and empirical datasets, we illustrate the large effects of different filtering thresholds on common population genetics statistics, such as Tajima’s D value, population differentiation (FST), nucleotide diversity (π) and effective population size (Ne). Filtering genomic data is a crucial step to ensure the quality and reliability of downstream analyses. The authors provide guidance on the choice of filtering strategies and thresholds, including filters that remove sequencing bases or reads, variants, loci, genotypes or individuals from genomic datasets to improve accuracy and reproducibility.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 11","pages":"750-767"},"PeriodicalIF":39.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0