Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “variational inference”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

Patterns of intraspecific diversification in the Piriqueta caroliniana complex in southeastern North America and the Bahamas.

We use chloroplast DNA (cpDNA) variation and nested clade phylogeographic analyses to infer the historical processes that have contributed to the high level of morphological and ecological diversification present in a group of herbaceous perennials (the Piriqueta caroliniana complex) in North America and the Bahamas. The presence of morphologically distinct and intercompatible varieties (morphotypes) that can be distinguished based on suites of taxonomic characters (e.g., leaf shape, pubescence type, stature) and contrasting habitat affinities (from marshes to dry pinelands and sand scrub) makes this group particularly appropriate for studies of intraspecific diversification. To examine the distribution of haplotypes among populations, we sampled 467 individuals from 55 locations in Florida, Georgia, and the northern Bahamas (Grand Bahama and Abaco) and screened each individual for cpDNA variation using restriction fragment length polymorphism (RFLP) and heteroduplex analyses. We develop a one-step haplotype phylogeny for this group and use the geographic distributions of haplotypes and clades to test specific phylogeographic hypotheses using the methods developed by Templeton and his colleagues (Templeton 1998). In general, the distribution of haplotypes was strongly influenced by limited dispersal distances, with the more recently derived haplotypes having much lower levels of dispersion and lower frequencies in populations than the ancestral haplotypes. The patterns of clade and haplotype dispersion and displacement and the distribution of morphotypes imply at least three cases of long-distance dispersal and one case of historical fragmentation. The historical patterns inferred for populations of Piriqueta are consistent with known biogeographical events, historical vegetation change, and the concordant patterns of multiple Pleistocene refugia that have been observed for a number of other taxa in southeastern North America.

Bahamas↗

The sexually-selected sperm hypothesis: sex-biased inheritance and sexual antagonism.

When females are inseminated by more than one male (polyandry) sexual selection continues after insemination in the form of sperm competition and cryptic female choice. The sexually-selected sperm hypothesis proposes that, under the risk of sperm competition, additive variation in male traits determining fertilising efficiency will select for female propensity to be polyandrous in order to increase the probability of producing sons with superior fertilising efficiency. Two factors complicate this prediction: sex-biased transmission of male fertilising efficiency traits and sexual antagonism of sex-limited traits, fostered by sex-biased inheritance. Here, we (i) review the evidence that male traits contributing towards fertilising efficiency are heritable through sex-biased mechanisms, and (ii) explore the evolutionary implications for male and female reproductive strategies caused by both sex-biased transmission and sexual antagonism of fertilising efficiency traits. Many male fertilising efficiency traits are heritable through sex-biased mechanisms and may not necessarily increase female fitness. The predictions of the sexually-selected sperm hypothesis change dramatically under these different mechanisms of inheritance of fertilising efficiency traits, and different fitness pay-offs derived by females from the expression of such traits. Both sex-biased control of fertilising efficiency and sexual antagonism may also be important in explaining the maintenance of the genetic variance and selection potential of fertilising efficiency. We propose that a useful approach to test the sexually-selected sperm hypothesis is to combine studies which identify behavioural and physiological mechanisms explaining variation in reproductive success with artificial selection experiments to infer the underlying evolutionary patterns.

Animals↗

Diurnal variation in precorneal tear film stability.

The stability of the precorneal tear film as inferred from the tear thinning time (TTT) appears to vary over a single 12-h period. The form of this variation is subject dependent. For the average patient the stability is low early in the morning, and tends to rise to equilibrium level between 10:00 a.m. and 12 noon.

Adult↗

Characterizing dynamic brain responses with fMRI: a multivariate approach.

In this paper we present a multivariate analysis of evoked hemodynamic responses and their spatiotemporal dynamics as measured with fast fMRI. This analysis uses standard multivariate statistics (MANCOVA) and the general linear model to make inferences about effects of interest and canonical variates analysis (CVA) to describe the important features of these effects. We have used these techniques to characterize the form of hemodynamic transients that are evoked during a cognitive or sensorimotor task. In particular we do not assume that the neural or hemodynamic response reaches some "steady state" but acknowledge that these physiological changes could show profound task-dependent adaptation and time-dependent changes during the task. To address this issue we have modeled hemodynamic responses using appropriate temporal basis functions and estimated their exact form within the general linear model using MANCOVA. We do not propose that this analysis is a particularly powerful way to make inferences about functional specialization (or more generally functional anatomy) because it only provides statistical inferences about the distributed (whole brain) responses evoked by different conditions. However, its application to characterizing the temporal aspects of evoked hemodynamic responses reveals some compelling and somewhat unexpected perspectives on transient but stereotyped responses to changes in cognitive or sensorimotor processing. The most remarkable observation is that these responses can be biphasic and show profound differences in their form depending on the extant task or condition. Furthermore these differences can be seen in the absence of changes in mean signal.

Arousal↗

Common pattern of evolution of gene expression level and protein sequence in Drosophila.

Sequence divergence scaled by variation within species has been used to infer the action of selection upon individual genes. Applying this approach to expression, we compared whole-genome whole-body RNA levels in 10 heterozygous Drosophila simulans genotypes and a pooled sample of 10 D. melanogaster lines using Affymetrix Genechip. For 972 genes expressed in D. melanogaster, the transcript level was below detection threshold in D. simulans, which may be explained either by sequence divergence between the primers on the chip and the mRNA transcripts or by down-regulation of these genes. Out of 6,707 genes that were expressed in both species, transcript level was significantly different between species for 534 genes (at P < 0.001). Genes whose expression is under stabilizing selection should exhibit reduced genetic variation within species and reduced divergence between species. Expression of genes under directional selection in D. simulans should be highly divergent from D. melanogaster, while showing low genetic variation in D. simulans. Finally, the genes with large variation within species but modest divergence between species are candidates for balancing selection. Rapidly diverging, low-polymorphism genes included those involved in reproduction (e.g., Mst 3Ba, 98Cb; Acps 26Aa, 63F; and sperm-specific dynein). Genes with high variation in transcript abundance within species included metallothionein and hairless, both hypothesized to be segregating in nature because of gene-by-environment interactions. Further, we compared expression divergence and DNA substitution rate in 195 genes. Synonymous substitution rate and expression divergences were uncorrelated, whereas there was a significant positive correlation between nonsynonymous substitution rate and expression divergence. We hypothesize that as a substantial fraction of nonsynonymous divergence has been shown to be adaptive, much of the observed expression divergence is likewise adaptive.

Amino Acid Sequence↗

Serum concentrations of gonadotropins and steroid hormones of Neophocaena phocaenoides asiaeorientalis in middle and lower regions of the Yangtze River.

As a relatively isolated and unique freshwater population, the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis) is the most endangered subpopulation of this species. The objective of this study was to improve our understanding of their reproductive endocrinology by measuring (radioimmunoassay) serum concentrations of FSH, LH, estradiol (E(2)), progesterone (P(4)) and testosterone (T(2)) in free-ranging animals. Blood samples were collected from 66 Yangtze finless porpoises (41 males and 25 females) captured in the middle and lower reaches of the Yangtze River. Based on significant variation of serum T(2) concentrations in males with body length (BL) >138 cm, we inferred that they were mature; in these animals, there were significant seasonal variations in serum T(2) concentrations, with the highest concentrations in March and April (502.0+/-319.8 ng/dL, mean+/-S.D.) and the lowest in December (79.4+/-83.2 ng/dL). Serum T(2) concentrations positively correlated with serum concentrations of LH and weakly correlated with serum concentrations of E(2), whereas there was a significant negative correlation between serum LH and FSH concentrations in males >138 cm. The smallest apparently pregnant female porpoise had a BL of 130 cm. Serum P(4) concentrations ranged from 13.2 to 112.4 ng/mL (43.9+/-28.3 ng/mL) in pregnant females, and fluctuated under 1.0 ng/mL in non-pregnant females with BL>130 cm. Serum LH concentrations were significantly higher in non-pregnant females >130 cm versus those females <130 cm. To our knowledge, this is the first study of endocrine-related maturity and seasonal breeding characteristics of the Yangtze finless porpoise.

Animals↗

The effect of filter size on VBM analyses of DT-MRI data.

Voxel-based morphometry (VBM) has been used to analyze diffusion tensor MRI (DT-MRI) data in a number of studies. In VBM, following spatial normalization, data are smoothed to improve the validity of statistical inferences and to reduce inter-individual variation. However, the size of the smoothing filter used for VBM of DT-MRI data is highly variable across studies. For example, a literature review revealed that Gaussian smoothing kernels ranging in size (full width at half maximum) from zero to 16 mm have been used in DT-MRI VBM type studies. To investigate the effect of varying filter size in such analyses, whole brain DT-MRI data from 14 schizophrenic patients were compared with those of 14 matched control subjects using VBM, when the filter size was varied from zero to 16 mm. Within this range of smoothing, four different conclusions regarding apparent patient control differences could be made: (i) no significant patient-control differences; (ii) reduced FA in right superior temporal gyrus (STG) in patients; (iii) reduced FA in both right STG and left cerebellum in patients; and (iv) reduced FA only in left cerebellum in patients. These findings stress the importance of recognizing the effect of the matched filter theorem on VBM analyses of DT-MRI data. Finally, we investigated whether one of the underlying assumptions of parametric VBM, i.e., the normality of the residuals, is met. Our results suggest that, even with moderate smoothing, a large number of voxels within central white matter regions may have non-normally distributed residuals thus making valid statistical inferences with a parametric approach problematic in these areas.

Adult↗

Founder mitochondrial haplotypes in Amerindian populations.

It had been proposed that the colonization of the New World took place by three successive migrations from northeastern Asia. The first one gave rise to Amerindians (Paleo-Indians), the second and third ones to Nadene and Aleut-Eskimo, respectively. Variation in mtDNA has been used to infer the demographic structure of the Amerindian ancestors. The study of RFLP all along the mtDNA and the analysis of nucleotide substitutions in the D-loop region of the mitochondrial genome apparently indicate that most or all full-blooded Amerindians cluster in one of four different mitochondrial haplotypes that are considered to represent the founder maternal lineages of Paleo-Indians. We have studied the mtDNA diversity in 109 Amerindians belonging to 3 different tribes, and we have reanalyzed the published data on 482 individuals from 18 other tribes. Our study confirms the existence of four major Amerindian haplotypes. However, we also found evidence supporting the existence of several other potential founder haplotypes or haplotype subsets in addition to the four ancestral lineages reported. Confirmation of a relatively high number of founder haplotypes would indicate that early migration into America was not accompanied by a severe genetic bottleneck.

Americas↗

Allelic and population variation of microsatellite loci in aspen (Populus tremuloides).

To develop a robust basis for inferences about population genetics and evolution, this work assayed 192 aspens (Populus tremuloides) from 11 sites in Wisconsin, USA, for allelic and population variation at 16 microsatellite loci distributed across the Populus genome. Frequency distributions of fluorochrome-labeled alleles resolved by capillary electrophoresis were analyzed for relationships to repeat size and number. Population-level statistics were compared with those of other studies, especially in Populus. All loci were polymorphic, varying widely in the number of alleles per locus (mean = 8.25, range 2-20). Expected and observed heterozygosities were high (0.45 and 0.41, respectively), with little differentiation among populations (F(ST) = 0.006-0.045) and a moderate level of inbreeding (F(IS) = 0.09), intermediate among levels reported in studies based on isozymes. Contrary to several other reports, allele frequencies clustered tightly around the modal frequency, and the genetic diversity (measured as alleles per locus or as expected heterozygosity) was not related to either the repeat unit size or to the number of repeats.

Alleles↗

Comparing evolvability and variability of quantitative traits.

There are two distinct reasons for making comparisons of genetic variation for quantitative characters. The first is to compare evolvabilities, or ability to respond to selection, and the second is to make inferences about the forces that maintain genetic variability. Measures of variation that are standardized by the trait mean, such as the additive genetic coefficient of variation, are appropriate for both purposes. Variation has usually been compared as narrow sense heritabilities, but this is almost always an inappropriate comparative measure of evolvability and variability. Coefficients of variation were calculated from 842 estimates of trait means, variances and heritabilities in the literature. Traits closely related to fitness have higher additive genetic and nongenetic variability by the coefficient of variation criterion than characters under weak selection. This is the reverse of the accepted conclusion based on comparisons of heritability. The low heritability of fitness components is best explained by their high residual variation. The high additive genetic and residual variability of fitness traits might be explained by the great number of genetic and environmental events they are affected by, or by a lack of stabilizing selection to reduce their phenotypic variance. Over one-third of the quantitative genetics papers reviewed did not report trait means or variances. Researchers should always report these statistics, so that measures of variation appropriate to a variety of situations may be calculated.

Animals↗

Analysis and exploration of the use of rule-based algorithms and consensus methods for the inferral of haplotypes.

The difficulty of experimental determination of haplotypes from phase-unknown genotypes has stimulated the development of nonexperimental inferral methods. One well-known approach for a group of unrelated individuals involves using the trivially deducible haplotypes (those found in individuals with zero or one heterozygous sites) and a set of rules to infer the haplotypes underlying ambiguous genotypes (those with two or more heterozygous sites). Neither the manner in which this "rule-based" approach should be implemented nor the accuracy of this approach has been adequately assessed. We implemented eight variations of this approach that differed in how a reference list of haplotypes was derived and in the rules for the analysis of ambiguous genotypes. We assessed the accuracy of these variations by comparing predicted and experimentally determined haplotypes involving nine polymorphic sites in the human apolipoprotein E (APOE) locus. The eight variations resulted in substantial differences in the average number of correctly inferred haplotype pairs. More than one set of inferred haplotype pairs was found for each of the variations we analyzed, implying that the rule-based approach is not sufficient by itself for haplotype inferral, despite its appealing simplicity. Accordingly, we explored consensus methods in which multiple inferrals for a given ambiguous genotype are combined to generate a single inferral; we show that the set of these "consensus" inferrals for all ambiguous genotypes is more accurate than the typical single set of inferrals chosen at random. We also use a consensus prediction to divide ambiguous genotypes into those whose algorithmic inferral is certain or almost certain and those whose less certain inferral makes molecular inferral preferable.

Algorithms↗

Variation of the ribosomal operon 16S-23S gene spacer region in representatives of Salmonella enterica subspecies.

The 16S-23S spacer regions of two ribosomal operons (rrnA and rrnE) have been sequenced in seven representatives of the Salmonella enterica subspecies. Isolated nucleotide substitutions were found at the same sites as in Escherichia coli but the number of polymorphic sites was much larger, as could be expected for a more heterogeneous species. Still, as in E. coli, most of the variation found was due to insertions and/or deletions affecting blocks of nucleotides generally located at equivalent regions of the putative secondary structure for both species. Isolated polymorphic sites generated phylogenetic trees generally consistent with the subspecies structure and the accepted relationships among the subspecies. However, the sequences of rrnE put subspecies I closer to E. coli K-12 than to the other S. enterica subspecies. The distribution of polymorphisms affecting blocks of nucleotides was much more random, and the presence of equivalent sequences in distantly related subspecies, and even in E. coli, could reflect relatively frequent horizontal transfer. The smallest 16S-23S spacers in other genera of the family Enterobacteriaceae were also sequenced. As expected, the level of variation was much larger. Still, the phylogenetic tree inferred is consistent with those of 16S rRNA or housekeeping genes.

Base Sequence↗

Phylogenetic analysis and trait evolution in Australian lineages of drywood termites (Isoptera, Kalotermitidae).

A phylogenetic analysis of Australian drywood termites (Isoptera, Kalotermitidae) based on partial sequence from the cytochrome oxidase II (COII) and cytochrome b genes is presented. In addition to providing new information on the evolutionary relationships among 25 species from seven genera, we evaluate the relative likelihoods of alternative topological hypotheses, including those derived from morphology-based classifications. We also test the applicability of a molecular clock for estimating the age of the Kalotermitidae and infer the evolution of species-specific variation for habitat type and soldier caste phragmosis by mapping this information onto the independently derived phylogeny. Maximum-likelihood analysis of both nucleotide and protein sequences from a multigene data set jointly support a single topology, which is shown to be the best estimate of the true phylogeny among the alternatives tested. Our results support the monophyly of all genera but question the discrimination between Procryptotermes and Cryptotermes. A basal dichotomy among generic groups suggests two principle lines of divergence within the family. Intergeneric relationships show mixed congruence to previous proposals, resulting in one morphology-based classification being rejected. A molecular clock hypothesis is not supported due to significant among-lineage rate heterogeneity in the COII gene. Patterns revealed through trait mapping suggest that the most recently diverged taxa tend to occupy the driest habitats and that these same taxa reflect a defensive transition away from large mandibulate soldiers toward small phragmotic soldiers. The association between habitat and defensibility supports the hypothesis that these two characters have been tightly linked throughout the social diversification of termites.

Animals↗

The relationship between executive functioning and verbal and visual learning and memory.

Executive functions, which include an individual's ability to develop a response set, inhibit behaviors, plan, and reason, likely impact other areas of cognitive functioning, such as learning and memory. The present study examined the relationship between executive functioning and a wide array of standardized, clinical verbal and visual learning and memory measures in 212 patients referred for a neuropsychological evaluation. IQ was also included in the analyses. Results of the canonical correlation analyses indicated that the two cognitive domains shared 55-60% of variance, and two canonical variates were present. Although causality cannot be inferred, a clear and robust relationship between executive functioning and memory is evident, and clinicians should consider this overlap when interpreting poor performance among these two domains.

Adolescent↗

The opioid receptor-ligand network in human cancers: pan-cancer multi-omics profiling and translational implications.

BACKGROUND: Opioid receptor-ligand signalling has been implicated in tumour biology and perioperative outcomes; however, its pan-cancer molecular landscape and clinical relevance remain incompletely defined. METHODS: We performed a pan-cancer multi-omics analysis of eight predefined opioid receptor-ligand genes across 33 tumour types from The Cancer Genome Atlas. Analyses included gene expression analysis using the linear models for microarray data (limma) package, genomic alterations, DNA methylation, regulatory network inference, pathway activity estimation using gene set variation analysis, and survival modelling. Multivariable Cox regression models were adjusted for age, sex, and tumour stage. RESULTS: Opioid receptor-ligand genes exhibited heterogeneous and generally low-to-moderate expression across tumour types. Genomic and epigenetic alterations were tumour-specific and variably associated with gene expression. Selected genes showed associations with overall survival in a tumour-dependent manner; however, these associations were attenuated after adjustment for clinical covariates and were accompanied by wide confidence intervals in some cohorts. Pathway analyses suggested associations with broader biological programmes, including epithelial-mesenchymal transition and immune-related pathways. Regulatory analyses identified candidate transcription factors and miRNAs, although these findings are exploratory. CONCLUSIONS: This pan-cancer analysis provides a systematic overview of opioid receptor-ligand gene features across human cancers. The observed associations are context-dependent and should be interpreted as hypothesis-generating. Further mechanistic and prospective studies are required to determine the clinical relevance of opioid signalling in cancer and perioperative settings.

Humans↗

Computational anatomy: shape, growth, and atrophy comparison via diffeomorphisms.

Computational anatomy (CA) is the mathematical study of anatomy I in I = I(alpha) o G, an orbit under groups of diffeomorphisms (i.e., smooth invertible mappings) g in G of anatomical exemplars I(alpha) in I. The observable images are the output of medical imaging devices. There are three components that CA examines: (i) constructions of the anatomical submanifolds, (ii) comparison of the anatomical manifolds via estimation of the underlying diffeomorphisms g in G defining the shape or geometry of the anatomical manifolds, and (iii) generation of probability laws of anatomical variation P(.) on the images I for inference and disease testing within anatomical models. This paper reviews recent advances in these three areas applied to shape, growth, and atrophy.

Algorithms↗

Relationships among Sarcocystis species transmitted by New World opossums (Didelphis spp.).

At least three species of Sarcocystis (S. neurona, S. falcatula, S. speeri) have recently been shown to use opossums of the genus Didelphis as their definitive host. In order to evaluate the evolutionary relationships among Sarcocystis spp. isolates from the Americas, and to determine whether organisms representing the same parasite lineages are transmitted north and south of the Panamanian isthmus, we inferred the phylogenetic relationships from nucleotide sequence variation in parasites isolated from three opossum species (D. virginiana, D. albiventris, D. marsupialis). In particular, we used variation in the 25/396 marker to compare several isolates from Brazil, Argentina, and the United States to each other and to cloned S. neurona and S. falcatula whose morphology and host affinities have been defined in the laboratory. S. neurona was identified from a Brazilian D. albiventris, as well as from North American D. virginiana. Parasites resembling the Cornell isolate of S. falcatula are transmitted both south and north of the Panamanian isthmus by D. albiventris and D. virginiana, respectively. Distinct attributes at two genetic loci differentiated a Brazilian isolate of S. falcatula from all other known parasite lineages. We confirm S. neurona as the causative agent of recently reported neurologic disease in Southern sea otters, Enhydra lutris nereis. And we found that S. speeri could not be compared to the other opossum-derived Sarcocystis isolates on the basis of nucleotide variation at the 25/396 locus. The widespread distribution of certain species of Sarcocystis may derive from their ability to parasitize migratory bird hosts in their intermediate stage.

Animals↗

GutenTag: high-throughput sequence tagging via an empirically derived fragmentation model.

Shotgun proteomics is a powerful tool for identifying the protein content of complex mixtures via liquid chromatography and tandem mass spectrometry. The most widely used class of algorithms for analyzing mass spectra of peptides has been database search software such as SEQUEST. A new sequence tag database search algorithm, called GutenTag, makes it possible to identify peptides with unknown posttranslational modifications or sequence variations. This software automates the process of inferring partial sequence "tags" directly from the spectrum and efficiently examines a sequence database for peptides that match these tags. When multiple candidate sequences result from the database search, the software evaluates which is the best match by a rapid examination of spectral fragment ions. We compare GutenTag's accuracy to that of SEQUEST on a defined protein mixture, showing that both modified and unmodified peptides can be successfully identified by this approach. GutenTag analyzed 33,000 spectra from a human lens sample, identifying peptides that were missed in prior SEQUEST analysis due to sequence polymorphisms and posttranslational modifications. The software is available under license; visit http://fields.scripps.edu for information.

Algorithms↗