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Results for “variational inference”

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At least 19 recordsLinked to original sources
PubMed2006

Genetics of sex-ratio variation inferred from parent-offspring regressions and sib correlations in the apple snail Pomacea canaliculata.

The brood sex ratio in the apple snail Pomacea canaliculata varies almost continuously from all male to all female, but the population sex ratio is nearly 1:1. In this study, regressions of the offspring sex ratio on the sex ratios of the parents' siblings as well as correlations in the brood sex ratios between sisters or brothers were investigated, in order to infer the genetic system that produces the sex-ratio pattern. There were significant positive relationships between the offspring sex ratio and the sex ratio of the mother's siblings (slope=0.28), and between the offspring sex ratios of two sisters (r=0.41). On the other hand, the father-offspring regression (slope=0.10), and the correlations between two brothers (r=-0.13) or between the brother and the sister (r=0.17) were not significant. These patterns differed from predictions using typical cytoplasmic sex factors, sex-ratio genes or sex-determining polygenes. Thus, the results suggest the involvement of either a small number of sex-determining genes or a more complicated system such as sex-ratio or sex-determining polygenes that act nonadditively.

Animals↗
PubMed2006

Variational Bayes inference of spatial mixture models for segmentation.

Mixture models are commonly used in the statistical segmentation of images. For example, they can be used for the segmentation of structural medical images into different matter types, or of statistical parametric maps into activating and nonactivating brain regions in functional imaging. Spatial mixture models have been developed to augment histogram information with spatial regularization using Markov random fields (MRFs). In previous work, an approximate model was developed to allow adaptive determination of the parameter controlling the strength of spatial regularization. Inference was performed using Markov Chain Monte Carlo (MCMC) sampling. However, this approach is prohibitively slow for large datasets. In this work, a more efficient inference approach is presented. This combines a variational Bayes approximation with a second-order Taylor expansion of the components of the posterior distribution, which would otherwise be intractable to Variational Bayes. This provides inference on fully adaptive spatial mixture models an order of magnitude faster than MCMC. We examine the behavior of this approach when applied to artificial data with different spatial characteristics, and to functional magnetic resonance imaging statistical parametric maps.

Algorithms↗
PubMed2004

Precision and accuracy of divergence time estimates from STR and SNPSTR variation.

Inference of intraspecific population divergence patterns typically requires genetic data for molecular markers with relatively high mutation rates. Microsatellites, or short tandem repeat (STR) polymorphisms, have proven informative in many such investigations. These markers are characterized, however, by high levels of homoplasy and varying mutational properties, often leading to inaccurate inference of population divergence. A SNPSTR is a genetic system that consists of an STR polymorphism closely linked (typically < 500 bp) to one or more single-nucleotide polymorphisms (SNPs). SNPSTR systems are characterized by lower levels of homoplasy than are STR loci. Divergence time estimates based on STR variation (on the derived SNP allele background) should, therefore, be more accurate and precise. We use coalescent-based simulations in the context of several models of demographic history to compare divergence time estimates based on SNPSTR haplotype frequencies and STR allele frequencies. We demonstrate that estimates of divergence time based on STR variation on the background of a derived SNP allele are more accurate (3% to 7% bias for SNPSTR versus 11% to 20% bias for STR) and more precise than STR-based estimates, conditional on a recent SNP mutation. These results hold even for models involving complex demographic scenarios with gene flow, population expansion, and population bottlenecks. Varying the timing of the mutation event generating the SNP revealed that estimates of divergence time are sensitive to SNP age, with more recent SNPs giving more accurate and precise estimates of divergence time. However, varying both mutational properties of STR loci and SNP age demonstrated that multiple independent SNPSTR systems provide less biased estimates of divergence time. Furthermore, the combination of estimates based separately on STR and SNPSTR variation provides insight into the age of the derived SNP alleles. In light of our simulations, we interpret estimates from data for human populations.

Data Interpretation, Statistical↗
PubMedDate not supplied

Genetic variation and inferences about perceived taste intensity in mice and men.

The study of genetic variation in taste produces parallels between mice and men. In mice, genetic variation across strains has been documented with psychophysical and anatomical measures as well as with recordings from whole nerves. In humans, the variation has been documented with psychophysical and anatomical measures. Whole-nerve recordings from animals and psychophysical ratings of perceived intensities from human subjects have a similar logical limitation: absolute comparisons across individuals require a standard stimulus that can be assumed equally intense to all. Comparisons across whole-nerve recordings are aided by single-fiber recordings. Comparisons across psychophysical ratings of perceived intensity have been aided by recent advances in methodology; these advances now reveal that the magnitude of genetic variation in human subjects is larger than previously suspected. In females, hormones further contribute to variation in taste. There is evidence that the ability to taste (particularly bitter) cycles with hormones in women of child-bearing age, rises to a maximum early in pregnancy and declines after menopause. Taste affects food preferences, which in turn affect dietary behavior and thus disease risks. Valid assessment of taste variation now permits measurement of the impact of taste variation on health. Advances in psychophysical methodology were essential to understanding genetic variation in taste. In turn, the association of perceived taste intensities with tongue anatomy now provides a new tool for psychophysics. The ability of a psychophysical scale to provide across-subject comparisons can be assessed through its ability to show the fungiform papillae density-taste association.

Animals↗
PubMed2004

Phylogeny and strain typing of Escherichia coli, inferred from variation at mononucleotide repeat loci.

Multilocus sequencing of housekeeping genes has been used previously for bacterial strain typing and for inferring evolutionary relationships among strains of Escherichia coli. In this study, we used shorter intergenic sequences that contained simple sequence repeats (SSRs) of repeating mononucleotide motifs (mononucleotide repeats [MNRs]) to infer the phylogeny of pathogenic and commensal E. coli strains. Seven noncoding loci (four MNRs and three non-SSRs) were sequenced in 27 strains, including enterohemorrhagic (six isolates of O157:H7), enteropathogenic, enterotoxigenic, B, and K-12 strains. The four MNRs were also sequenced in 20 representative strains of the E. coli reference (ECOR) collection. Sequence polymorphism was significantly higher at the MNR loci, including the flanking sequences, indicating a higher mutation rate in the sequences flanking the MNR tracts. The four MNR loci were amplifiable by PCR in the standard ECOR A, B1, and D groups, but only one (yaiN) in the B2 group was amplified, which is consistent with previous studies that suggested that B2 is the most ancient group. High sequence compatibility was found between the four MNR loci, indicating that they are in the same clonal frame. The phylogenetic trees that were constructed from the sequence data were in good agreement with those of previous studies that used multilocus enzyme electrophoresis. The results demonstrate that MNR loci are useful for inferring phylogenetic relationships and provide much higher sequence variation than housekeeping genes. Therefore, the use of MNR loci for multilocus sequence typing should prove efficient for clinical diagnostics, epidemiology, and evolutionary study of bacteria.

Bacterial Typing Techniques↗
PubMed1999

The use of microsatellite variation to infer population structure and demographic history in a natural model system.

To assess the reliability of genetic markers it is important to compare inferences that are based on them to a priori expectations. In this article we present an analysis of microsatellite variation within and among populations of island foxes (Urocyon littoralis) on California's Channel Islands. We first show that microsatellite variation at a moderate number of loci (19) can provide an essentially perfect description of the boundaries between populations and an accurate representation of their historical relationships. We also show that the pattern of variation across unlinked microsatellite loci can be used to test whether population size has been constant or increasing. Application of these approaches to the island fox system indicates that microsatellite variation may carry considerably more information about population history than is currently being used.

Animals↗
PubMed2003

Variational Bayesian inference for fMRI time series.

We describe a Bayesian estimation and inference procedure for fMRI time series based on the use of General Linear Models with Autoregressive (AR) error processes. We make use of the Variational Bayesian (VB) framework which approximates the true posterior density with a factorised density. The fidelity of this approximation is verified via Gibbs sampling. The VB approach provides a natural extension to previous Bayesian analyses which have used Empirical Bayes. VB has the advantage of taking into account the variability of hyperparameter estimates with little additional computational effort. Further, VB allows for automatic selection of the order of the AR process. Results are shown on simulated data and on data from an event-related fMRI experiment.

Algorithms↗
PubMed1996

Phonological variation and inference in lexical access.

Recent experiments have indicated that lexical access in speech is highly intolerant of mismatch. An isolated sequence such as [symbol: see text] strongly disrupts access to the underlying lexical entry (wicked). This observation seems inconsistent with the systematic variability found in the phonetic form of words. Two cross-modal priming experiments tested the hypothesis that phonologically regular variation is perceptually acceptable. Participants heard tokens like [symbol: see text] embedded in contexts that either licensed the change as a result of a regular assimilation process (e.g., [symbol: see text]) or rendered the change phonologically unviable (e.g., [symbol: see text]). The tokens with contextually unviable deviations did not effectively access lexical representations. In contrast, the same tokens in viable phonological context primed as strongly as unchanged controls. These results suggest that mapping speech onto lexical representations involves on-line phonological inference.

Adolescent↗
PubMed2026

Accounting for recombination rate variation improves inference of barrier loci and reveals the role of both natural and sexual selection in an incipient bird radiation.

Examining genomic patterns of differentiation across lineage pairs at different stages of the speciation continuum, in combination with recombination maps, can help disentangle the effects of linked and divergent selection and identify lineage-specific targets of selection that may act as barrier loci during speciation. Here, we apply this framework to genomic data from African and Indian Ocean bird species of the genus Zosterops (Zosteropidae) to identify candidate barrier loci between ecologically, phenotypically, and genetically distinct Reunion gray white-eye (Zosterops borbonicus) parapatric geographic forms. Using analyses that account for recombination rate variation, we show that putative targets of divergent selection are primarily located on the Z chromosome, except in comparisons between geographic forms that differ in their ecologies. Functional annotation revealed that candidate barrier loci between forms with similar environmental niches are associated with genes involved in song formation and immune function, whereas those between forms with different environmental niches are associated with adaptation to altitude, morphology, and song behavior. Our results highlight the combined roles of natural and sexual selection in the evolution of reproductive barriers in this incipient species radiation.

Animals↗
PubMed2005

Incorporating gene-specific variation when inferring and evaluating optimal evolutionary tree topologies from multilocus sequence data.

Because of the increase of genomic data, multiple genes are often available for the inference of phylogenetic relationships. The simple approach for combining multiple genes from the same taxon is to concatenate the sequences and then ignore the fact that different positions in the concatenated sequence came from different genes. Here, we discuss two criteria for inferring the optimal tree topology from data sets with multiple genes. These criteria are designed for multigene data sets where gene-specific evolutionary features are too important to ignore. One criterion is conventional and is obtained by taking the sum of log-likelihoods over all genes. The other criterion is obtained by dividing the log-likelihood for a gene by its sequence length and then taking the arithmetic mean over genes of these ratios. A similar strategy could be adopted with parsimony scores. The optimal tree is then declared to be the one for which the sum or the arithmetic mean is maximized. These criteria are justified within a two-stage hierarchical framework. The first level of the hierarchy represents gene-specific evolutionary features, and the second represents site-specific features for given genes. For testing significance of the optimal topology, we suggest a two-stage bootstrap procedure that involves resampling genes and then resampling alignment columns within resampled genes. An advantage of this procedure over concatenation is that it can effectively account for gene-specific evolutionary features. We discuss the applicability of the two-stage bootstrap idea to the Kishino-Hasegawa test and the Shimodaira-Hasegawa test.

Biological Evolution↗
PubMed2000

A phylogenetic view on species radiation in Apodemus inferred from variation of nuclear and mitochondrial genes.

Species of field mice (genus Apodemus) are the most common rodents inhabiting woodlands and forests of the Palaearctic region. We examined the cytochrome b (cyt b) gene in mitochondrial DNA (1140 bp) and the interphotoreceptor retinoid binding protein (IRBP) gene in nuclear DNA (1152 bp) in nine species of Apodemus. Based on the genetic variation, the nine species were grouped into four lineages: (1) Agrarius group (A. agrarius, A. peninsulae, A. semotus, and A. speciosus), (2) Argenteus group (A. argenteus), (3) Gurkha group (A. gurkha), and (4) Sylvaticus group (A. alpicola, A. flavicollis, and A. sylvaticus). It was shown that these four lineages diverged within a short period of evolutionary time, suggestive of a radiation event. Soon after the radiation, the Agrarius group was likely to have differentiated again into the species lineages simultaneously. In contrast, the European clade, the Sylvaticus group, radiated rather recently. The relative ratio of the extent of sequence divergence among the four main lineages to that among the members of the subfamily Murinae (including Mus and Rattus) was calculated to be 72.4% in the cyt b gene with transversional substitutions, and 58.5% in the IRBP gene with all substitutions, using the Kimura two-parameter method. The value for the three European lineages was 27.6% in the cyt b gene and 12.3% in the IRBP gene. These results may have a correlation with the notion that deciduous broadleaf forests remained in Central East Asia through the late Tertiary to the present, while those in Europe to a large extent had disappeared by the Pliocene.

Animals↗
PubMed2003

Phylogeography and population structure of the common warthog (Phacochoerus africanus) inferred from variation in mitochondrial DNA sequences and microsatellite loci.

Global climate fluctuated considerably throughout the Pliocene and Pleistocene, influencing the evolutionary history of a wide range of species. Using both mitochondrial sequences and microsatellites, we have investigated the evolutionary consequences of such environmental fluctuation for the patterns of genetic variation in the common warthog, sampled from 24 localities in Africa. In the sample of 181 individuals, 70 mitochondrial DNA haplotypes were identified and an overall nucleotide diversity of 4.0% was observed. The haplotypes cluster in three well-differentiated clades (estimated net sequence divergence of 3.1-6.6%) corresponding to the geographical origins of individuals (i.e. eastern, western and southern African clades). At the microsatellite loci, high polymorphism was observed both in the number of alleles per locus (6-21), and in the gene diversity (in each population 0.59-0.80). Analysis of population differentiation indicates greater subdivision at the mitochondrial loci (FST=0.85) than at nuclear loci (FST=0.20), but both mitochondrial and nuclear loci support the existence of the three warthog lineages. We interpret our results in terms of the large-scale climatic fluctuations of the Pleistocene.

Animals↗
PubMed2004

Gene expression, synteny, and local similarity in human noncoding mutation rates.

The human genome is organized with regard to many features such as isochores, Giemsa bands, clusters of genes with similar expression patterns, and contiguous regions with shared evolutionary histories (synteny blocks). In addition to these genomic features, it is clear that mutation rates also vary across the human genome. To address how mutation rates and genomic features are related, we analyzed substitution rates at three classes of putatively neutral noncoding sites (nongenic, intronic, and ancestral repeats) in approximately 14 Mb of human-chimpanzee alignments covering human chromosome 7. Patterns of mutation rate variation inferred from substitution rate variation differ among the three site classes. In particular, we find that intronic mutation rates are strongly affected by the breadth of expression of the genes in which they reside, with broadly expressed genes exhibiting low mutation rates, probably as a consequence of the transcription-coupled repair process acting in the germ line. All site classes show significant local similarities in mutation rate at the megabase scale, and regional similarities in nongenic mutation rate covary with blocks of synteny between the human and mouse genomes, indicating that the evolutionary history of a genomic region is an important determinant of mutation rate.

Animals↗
PubMed1997

RNA aptamers to the adenosine moiety of S-adenosyl methionine: structural inferences from variations on a theme and the reproducibility of SELEX.

We used in vitro selection (SELEX) to isolate RNA 'aptamers' to S-adenosyl methionine (SAM). Individual aptamer sequences conform to the structural element noted previously for adenosine binding in selections for aptamers to ATP and NAD+. When we compare the patterns of sequence conservation among 65 adenosine-binding sequences to the published structure of the adenosine aptamer, we find that the most highly conserved nucleotides contact the bound adenosine directly, and that one conserved nucleotide outside the binding pocket is in position to stabilize nucleotides within the binding pocket. The aptamer's ability to bind diverse adenosine-containing cofactors is easily understood in terms of its mode of binding, which leaves the 5'position exposed to solvent. We propose that aptamers that bind their targets away from the reactive moiety may be particularly well suited for catalysis. Finally, we estimate that one sequence in 10(11) may be able to form this structural motif, and that there may be many other adenosine-binding motifs that have escaped detection because of their lower representation in the starting random pools.

Adenosine↗
PubMed1984

Genetic relationships between subspecies of the tsetse fly Glossina morsitans inferred from variation in mitochondrial DNA sequences.

A 750 base pair segment of DNA from the tsetse fly Glossina morsitans morsitans was isolated by means of molecular cloning. It was shown by DNA hybridization to have substantial sequence homology with a defined region of the mitochondrial genomes of several Drosophila species. When used as a probe against DNA prepared from single tsetse flies, the cloned sequence revealed local restriction site variation between members of the G. morsitans subspecies complex. This feature was used to demonstrate maternal inheritance of the sequence in progeny of hybrid crosses and to assemble comparative restriction maps for a 3-kilobase segment of each mitochondrial genome. The data obtained from these exercises point to a higher genetic identity between G. m. morsitans and G. m. centralis than between either form and G. m. submorsitans.

Animals↗
PubMed2003

Ribosomal dynamics inferred from variations in experimental measurements.

The crystal structures of the ribosome reveal remarkable complexity and provide a starting set of snapshots with which to understand the dynamics of translation. To augment the static crystallographic models with dynamic information present in crosslink, footprint, and cleavage data, we examined 2691 proximity measurements and focused on the subset that was apparently incompatible with >40 published crystal structures. The measurements from this subset generally involve regions of the structure that are functionally conserved and structurally flexible. Local movements in the crystallographic states of the ribosome that would satisfy biochemical proximity measurements show coherent patterns suggesting alternative conformations of the ribosome. Three different types of data obtained for the two subunits display similar "mismatching" patterns, suggesting that the signals are robust and real. In particular, there is an indication of coherent motion in the decoding region within the 30S subunit and central protuberance and surrounding areas of the 50S subunit. Directions of rearrangements fluctuate around the proposed path of tRNA translocation and the plane parallel to the interface of the two subunits. Our results demonstrate that systematic combination and analysis of noisy, apparently incompatible data sources can provide biologically useful signals about structural dynamics.

Crystallography, X-Ray↗
PubMed2001

Speciation in a ring.

The evolutionary divergence of a single species into two has never been directly observed in nature, primarily because speciation can take a long time to occur. A ring species, in which a chain of intergrading populations encircles a barrier and the terminal forms coexist without interbreeding, provides a situation in which variation in space can be used to infer variation in time. Here we reconstruct the pathway to speciation between two reproductively isolated forms of greenish warbler (Phylloscopus trochiloides). These two taxa do not interbreed in central Siberia but are connected by a long chain of intergrading populations encircling the Tibetan Plateau to the south. Molecular data and climatic history imply that the reproductively isolated taxa came into contact following expansions northward around the western and eastern sides of the plateau. Parallel selection pressures for increased song complexity during the northward expansions have been accompanied by divergence in song structure. Playback experiments show that the two Siberian forms do not recognize each other's songs. Our results show how gradual divergence in a trait involved in mate choice leads to the formation of new species.

Animals↗
PubMed2026

Unifying multimodal single-cell data with a mixture-of-experts &#x3b2;-variational autoencoder framework.

Multimodal single-cell assays profile complementary layers of cell state, but integration is complicated by modality mismatch, sparsity, and uneven cohort coverage. Here, we present Unified Variational Inference (UniVI), a scalable mixture-of-experts &#x3b2;-variational autoencoder that learns a shared latent space while preserving modality-specific structure. UniVI couples modality-specific encoders/decoders with a shared latent prior and a symmetric cross-modal alignment objective, enabling consistent integration of paired measurements without curated feature-link graphs or preannotated reference atlases; optional supervised heads can be added when labels are available. Across paired RNA-protein (CITE-seq) and RNA-chromatin (10x Genomics Multiome, SHARE-seq) data spanning human PBMCs and mouse back skin-a nonhematopoietic tissue with continuous differentiation hierarchies-UniVI produces coherent embeddings, improves label transfer, and enables cross-modal reconstruction and denoising. Extending to trimodal measurements, UniVI maintains robust three-way alignment among RNA, chromatin accessibility, and surface proteins (TEA-seq), and accommodates DNA methylation in a paired scNMT-seq mouse gastrulation proof-of-concept under beta-binomial likelihoods. Performance degrades gracefully under severe cell type imbalance and in the presence of modality-exclusive populations. In an acute myeloid leukemia mosaic design, a paired RNA-protein bridge anchors independent RNA-only and protein+genotype cohorts, revealing genotype-associated neighborhoods that sharpen with mutation-aware fine-tuning. UniVI thus provides a flexible, interpretable framework for multimodal integration across paired, trimodal, and mosaic study designs and supports practical reference-to-query projection in partially observed studies.

Journal Article↗