Biomedical subjects

Xiaoquan Wen

Publications and source records attributed to Xiaoquan Wen.

6 recordsLinked to original sources

PubMed2026

Diagnosing scientific replicability through probabilistic distinguishability.

MOTIVATION: Despite the widely recognized importance of replicability in biological research, computational methods to quantify irreplicability and identify irreplicable instances remain underdeveloped. This article presents an efficient and robust computational framework to address this gap. RESULTS: To tackle the challenge of defining an acceptable level of intrinsic heterogeneity among replicable studies, we introduce a distinguishability criterion, ensuring that replicable effects, while potentially heterogeneous, can be distinguished from zero effects and maintain consistent directions with high probability. We implement a Bayesian model criticism approach, reporting a Bayesian P-value to identify potential irreplicable instances. Through numerical experiments, we demonstrate the efficacy of the proposed methods in detecting batch effects in high-throughput experiments and identifying instances of the publication bias. Finally, we apply the framework to multi-tissue eQTL data from the GTEx consortium, uncovering tissue-specific eQTLs that represent biological heterogeneity across tissues. AVAILABILITY AND IMPLEMENTATION: An R package DiscRep implementing our method is available on GitHub (https://github.com/PengWang96/DiscRep).

Bayes Theorem↗

PubMed2006

A worldwide survey of haplotype variation and linkage disequilibrium in the human genome.

Recent genomic surveys have produced high-resolution haplotype information, but only in a small number of human populations. We report haplotype structure across 12 Mb of DNA sequence in 927 individuals representing 52 populations. The geographic distribution of haplotypes reflects human history, with a loss of haplotype diversity as distance increases from Africa. Although the extent of linkage disequilibrium (LD) varies markedly across populations, considerable sharing of haplotype structure exists, and inferred recombination hotspot locations generally match across groups. The four samples in the International HapMap Project contain the majority of common haplotypes found in most populations: averaging across populations, 83% of common 20-kb haplotypes in a population are also common in the most similar HapMap sample. Consequently, although the portability of tag SNPs based on the HapMap is reduced in low-LD Africans, the HapMap will be helpful for the design of genome-wide association mapping studies in nearly all human populations.

Chromosome Mapping↗

PubMed2006

Coverage and characteristics of the Affymetrix GeneChip Human Mapping 100K SNP set.

Improvements in technology have made it possible to conduct genome-wide association mapping at costs within reach of academic investigators, and experiments are currently being conducted with a variety of high-throughput platforms. To provide an appropriate context for interpreting results of such studies, we summarize here results of an investigation of one of the first of these technologies to be publicly available, the Affymetrix GeneChip Human Mapping 100K set of single nucleotide polymorphisms (SNPs). In a systematic analysis of the pattern and distribution of SNPs in the Mapping 100K set, we find that SNPs in this set are undersampled from coding regions (both nonsynonymous and synonymous) and oversampled from regions outside genes, relative to SNPs in the overall HapMap database. In addition, we utilize a novel multilocus linkage disequilibrium (LD) coefficient based on information content (analogous to the information content scores commonly used for linkage mapping) that is equivalent to the familiar measure r2 in the special case of two loci. Using this approach, we are able to summarize for any subset of markers, such as the Affymetrix Mapping 100K set, the information available for association mapping in that subset, relative to the information available in the full set of markers included in the HapMap, and highlight circumstances in which this multilocus measure of LD provides substantial additional insight about the haplotype structure in a region over pairwise measures of LD.

Chromosome Mapping↗

PubMed2006

A map of recent positive selection in the human genome.

The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP) data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

Alleles↗

PubMed2005

Association mapping and fine mapping with TreeLD.

SUMMARY: The program package TreeLD implements a unified approach to association mapping and fine mapping of complex trait loci and a novel approach to visualizing association data, based on an inferred ancestry of the sample. Fundamentally, the TreeLD approach is based on the idea that the evidence for association at a particular position is contained in the ancestral tree relating the sampled chromosomes at that position. TreeLD provides an easy-to-use interface and can be applied to case-control, TDT trio and quantitative trait data.

Algorithms↗

PubMed2003

Evidence for extensive transmission distortion in the human genome.

It is a basic principle of genetics that each chromosome is transmitted from parent to offspring with a probability that is given by Mendel's laws. However, several known biological processes lead to skewed transmission probabilities among surviving offspring and, therefore, to excess genetic sharing among relatives. Examples include in utero selection against deleterious mutations, meiotic drive, and maternal-fetal incompatibility. Although these processes affect our basic understanding of inheritance, little is known about their overall impact in humans or other mammals. In this study, we examined genome screen data from 148 nuclear families, collected without reference to phenotype, to look for departures from Mendelian transmission proportions. Using single-point and multipoint linkage analysis, we detected a modest but significant genomewide shift towards excess genetic sharing among siblings (average sharing of 50.43% for the autosomes; P=.009). Our calculations indicate that many loci with skewed transmission are required to produce a genomewide shift of this magnitude. Since transmission distortion loci are subject to strong selection, this raises interesting questions about the evolutionary forces that keep them polymorphic. Finally, our results also have implications for mapping disease genes and for the genetics of fertility.

Chromosome Mapping↗