共查询到13条相似文献,搜索用时 0 毫秒
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Whole-genome sequences provide a rich source of information about human evolution. Here we describe an effort to estimate key evolutionary parameters based on the whole-genome sequences of six individuals from diverse human populations. We used a Bayesian, coalescent-based approach to obtain information about ancestral population sizes, divergence times and migration rates from inferred genealogies at many neutrally evolving loci across the genome. We introduce new methods for accommodating gene flow between populations and integrating over possible phasings of diploid genotypes. We also describe a custom pipeline for genotype inference to mitigate biases from heterogeneous sequencing technologies and coverage levels. Our analysis indicates that the San population of southern Africa diverged from other human populations approximately 108-157 thousand years ago, that Eurasians diverged from an ancestral African population 38-64 thousand years ago, and that the effective population size of the ancestors of all modern humans was ~9,000. 相似文献
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Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data 总被引:40,自引:0,他引:40
Segal E Shapira M Regev A Pe'er D Botstein D Koller D Friedman N 《Nature genetics》2003,34(2):166-176
Much of a cell's activity is organized as a network of interacting modules: sets of genes coregulated to respond to different conditions. We present a probabilistic method for identifying regulatory modules from gene expression data. Our procedure identifies modules of coregulated genes, their regulators and the conditions under which regulation occurs, generating testable hypotheses in the form 'regulator X regulates module Y under conditions W'. We applied the method to a Saccharomyces cerevisiae expression data set, showing its ability to identify functionally coherent modules and their correct regulators. We present microarray experiments supporting three novel predictions, suggesting regulatory roles for previously uncharacterized proteins. 相似文献
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Mehrabian M Allayee H Stockton J Lum PY Drake TA Castellani LW Suh M Armour C Edwards S Lamb J Lusis AJ Schadt EE 《Nature genetics》2005,37(11):1224-1233
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An integrative genomics approach to infer causal associations between gene expression and disease 总被引:2,自引:0,他引:2
Schadt EE Lamb J Yang X Zhu J Edwards S Guhathakurta D Sieberts SK Monks S Reitman M Zhang C Lum PY Leonardson A Thieringer R Metzger JM Yang L Castle J Zhu H Kash SF Drake TA Sachs A Lusis AJ 《Nature genetics》2005,37(7):710-717
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A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers 总被引:2,自引:0,他引:2
We developed a computational method to characterize aneuploidy in tumor samples based on coordinated aberrations in expression of genes localized to each chromosomal region. We summarized the total level of chromosomal aberration in a given tumor in a univariate measure termed total functional aneuploidy. We identified a signature of chromosomal instability from specific genes whose expression was consistently correlated with total functional aneuploidy in several cancer types. Net overexpression of this signature was predictive of poor clinical outcome in 12 cancer data sets representing six cancer types. Also, the signature of chromosomal instability was higher in metastasis samples than in primary tumors and was able to stratify grade 1 and grade 2 breast tumors according to clinical outcome. These results provide a means to assess the potential role of chromosomal instability in determining malignant potential over a broad range of tumors. 相似文献
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In model organisms, chemical mutagenesis provides a powerful alternative to natural, polygenic variation (for example, quantitative trait loci (QTLs)) for identifying functional pathways and complex disease genes. Despite recent progress in QTLs, we expect that mutagenesis is will ultimately prove more effective because the prospects of gene identification are high and every gene affecting a trait is potentially a target. 相似文献