ArticleGenetics2011
Inference of site frequency spectra from high-throughput sequence data: quantification of selection on nonsynonymous and synonymous sites in humans.
Article in Genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed.
- Why there are so many definitions of fitness in models.Genetics · 2026Review
- CoalMiner: a coalescent model generator forbioRxiv : the preprint server for biology · 2026Article
- The impact of non-neutral synonymous mutations when inferring selection on nonsynonymous mutations.Genetics · 2025Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- distAngsd: Fast and Accurate Inference of Genetic Distances for Next-Generation Sequencing Data.Molecular biology and evolution · 2022Article
- Nonsynonymous Polymorphism Counts in Bacterial Genomes: a Comparative Examination.Applied and environmental microbiology · 2020Article
- Natural Selection Shapes Codon Usage in the Human Genome.American journal of human genetics · 2020Article
- Exonic splice regulation imposes strong selection at synonymous sites.Genome research · 2018Article
- Genomic data reveal a loss of diversity in two species of tuco-tucos (genus Ctenomys) following a volcanic eruption.Scientific reports · 2017Article
- Estimating the prevalence of functional exonic splice regulatory information.Human genetics · 2017Review
- Review
- Are Synonymous Sites in Primates and Rodents Functionally Constrained?Journal of molecular evolution · 2016Article
- Article
- Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations.PLoS computational biology · 2015Article
- Evidence for increased levels of positive and negative selection on the X chromosome versus autosomes in humans.Molecular biology and evolution · 2014Article
- Genome-wide estimation of linkage disequilibrium from population-level high-throughput sequencing data.Genetics · 2014Article
- Population genetic analysis of bi-allelic structural variants from low-coverage sequence data with an expectation-maximization algorithm.BMC bioinformatics · 2014Article
- Comparative population genomics: power and principles for the inference of functionality.Trends in genetics : TIG · 2014Review
- The impact of whole-genome sequencing on the reconstruction of human population history.Nature reviews. Genetics · 2014Review
- Characterizing bias in population genetic inferences from low-coverage sequencing data.Molecular biology and evolution · 2014Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Sequencing errors and random sampling of nucleotide types among sequencing reads at heterozygous sites present challenges for accurate, unbiased inference of single-nucleotide polymorphism genotypes from high-throughput sequence data. Here, we develop a maximum-likelihood approach to estimate the frequency distribution of the number of alleles in a sample of individuals (the site frequency spectrum), using high-throughput sequence data. Our method assumes binomial sampling of nucleotide types in heterozygotes and random sequencing error. By simulations, we show that close to unbiased estimates of the site frequency spectrum can be obtained if the error rate per base read does not exceed the population nucleotide diversity. We also show that these estimates are reasonably robust if errors are nonrandom. We then apply the method to infer site frequency spectra for zerofold degenerate, fourfold degenerate, and intronic sites of protein-coding genes using the low coverage human sequence data produced by the 1000 Genomes Project phase-one pilot. By fitting a model to the inferred site frequency spectra that estimates parameters of the distribution of fitness effects of new mutations, we find evidence for significant natural selection operating on fourfold sites. We also find that a model with variable effects of mutations at synonymous sites fits the data significantly better than a model with equal mutational effects. Under the variable effects model, we infer that 11% of synonymous mutations are subject to strong purifying selection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.