Biology subjects

Wu, Y.

Publications and source records attributed to Wu, Y..

At least 1,063 records · Page 59Linked to original sources

bioRxiv2018

Investigation of novel functions of three genes in oriental river prawn, Macrobrachium nipponense: Molecular Cloning, Expression, and In situ Hybridization Analysis

Three genes were predicted to be potentially involved in the male sexual development in M. nipponense, including the Gem-associated protein 2-like isoform X1 (GEM), Ferritin peptide, and DNA polymerase zeta catalytic subunit (Rev3). In this study, we aimed to investigate their novel functions in depth. The full-length cDNA sequence of Mn-GEM was 1,018 bp, encoding 258 amino acids. The partial Mn-Rev3 cDNA sequence was 6,832 bp, encoding 1,203 amino acids. Tissue distribution indicated that all of these three genes have higher expression level in testis and androgenic gland, implying their novel functions in male sexual development. In situ hybridization analysis further confirmed the novel roles of these three genes. Rev3 promote the testis development during the whole reproductive cycle, while GEM and ferritin only promote the activation of testis development. Besides, these three genes play essential roles in funicular structure development surrounding the androgenic gland cells, which promote and support the formation of androgenic gland cells. The expression in hepatopancreas cells also suggested their role in immune system in M. nipponense. This study advances our understanding of male sexual development in M. nipponense, as well as providing the basis for further studies of male sexual differentiation and development in crustaceans.

zoology↗

bioRxiv2018

An \"inverse approach\" to the treatment of amblyopia

Recent laboratory finding suggest that short-term patching the amblyopic eye (i.e., inverse occlusion) results in a larger and more sustained improvement in the binocular balance compared with normal controls. In this study, we investigate the cumulative effects of the short-term inverse occlusion in adults and old children with amblyopia. A prospective cohort study of 18 amblyopes (10-35 years old; 3 with strabismus) who have been subjected to 2 hours/day of inverse occlusion for 2 months. Patients who required refractive correction or whose refractive correction needed updating were given a 2-month period of refractive adaptation. The primary outcome measure was the binocular balance which was measured using a phase combination task, the secondary outcome measures were the best corrected visual acuity which was measured with a Tumbling E acuity chart and convert to logMAR units and the stereo acuity which was measured with the Random-dot preschool stereotest. The averaged binocular gain was 0.11 in terms of the effective contrast ratio (z = -2.344, p = 0.019, 2-tailed Related samples Wilcoxon Signed Ranks Test). The average acuity gain was 0.14 logMAR equivalent (t(17) = 0.13, p < 0.001, 2-tailed paired samples t-test). The averaged stereo acuity gain was 253 arc seconds (z = -2.689, p = 0.007). Based on more recent research concerning adult ocular dominance plasticity, contrary to current practice, patching the amblyopic eye makes more sense; comparable acuity benefits, better compliance, better binocular outcome and applicable to adults as well as old children.

neuroscience↗

bioRxiv2018

Characterisation and development of aspirin inducible biosensors in E. coli Nissle 1917 and SimCells

A simple aspirin-inducible system has been developed by employing the Psal promoter and SalR regulation system originally from Acinetobacter baylyi ADP1, which has been cloned into E. coli for characterisation of gene circuits and induction of novel SimCells (simple cells). Mutagenesis at the DNA binding domain (DBD) and chemical recognition domain (CRD) of the SalR protein in A. baylyi ADP1 suggests that inactive SalRi can compete with activated SalRa, occupying the binding position of Psal promoter. The induction of the Psal promoter was compared in two different designs in E. coli: simple regulation (SRS) and positive autoregulated system (PAR). Both regulatory systems were induced in a dose-dependent manner in the presence of aspirin in the range of 0.05-10 M. Over-expression of SalR in the SRS system reduces both baseline leakiness and inducible strength of Psal promoter. A weak SalR expression significantly improve the inducible strength, which is in a good agreement of the proposed hypothesis of SalRi/SalRa competitive binding. The PAR system provides a feedback loop that fine-tunes the level of SalR, displaying inducible strength. A mathematical model based on SalRi/SalRa competitive binding hypothesis was developed, which not only reproduces the observed experimental results but also predict the performance of a new gene circuit design. The aspirin-inducible systems were also functional in probiotic strain E.coli Nissle 1917 (EcN) and SimCells produced from E. coli MC1000 {Delta}minD. The well-characterised and modularised aspirin-inducible gene circuits would be useful biobricks for bacterial therapy in environment and medical applications.

microbiology↗

bioRxiv2018

Vitamin A supplement after neonatal Streptococcus pneumoniae pneumonia alters CD4+T cell subset and inhibits allergic asthma in mice model

BackgroundPreviously, we showed that neonatal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) promoted adulthood ovalbumin (OVA) induced allergic asthma. Many studies have demonstrated that vitamin A deficiency induced the development of allergic asthma. Whether neonatal S. pneumoniae pneumonia promoted allergic asthma development was associated with vitamin A concentrations remains unclear.\n\nMethodsFemale BALB/c neonates were infected with S. pneumoniae strain D39 and subsequently treated with vitamin A. Vitamin A concentrations in lung, serum and liver were monitored on 2, 5, 7, 14, 21, 28 days post infection. Four weeks after infection, mice were sensitized and challenged with OVA to induce allergic airway disease (AAD) in early adulthood. Twenty-four hours after the final challenge, lung histo-pathology, cytokine concentrations in bronchoalveolar lavage fluid (BALF), airway hyperresponsiveness (AHR) and lung CD4+T cells were measured.\n\nResultsWe demonstrated that neonatal S. pneumoniae pneumonia induce lung vitamin A deficiency up to early adulthood. Moreover, neonatal S. pneumoniae pneumonia aggravated airway inflammatory cells accumulation and increased AHR during AAD, decreased Foxp3+Treg and Th1 productions remarkably, while Th2 cell expression was increased significantly. Further study indicated that vitamin A supplement after neonatal S. pneumoniae pneumonia can promote Foxp3+Treg and Th1 productions, decrease Th2 cell expressions, alleviate AHR and inflammatory cells infiltration during AAD.\n\nConclusionsUsing a mouse model, we demonstrate that Vitamin A supplement after neonatal Streptococcus pneumoniae pneumonia alters the CD4+T cell subset and inhibits the development of early adulthood allergic asthma.

immunology↗

bioRxiv2018

Tibetan antelope rests like a Puppet

AbstractRest contributes to a large part of animals daily life, and animals usually rest in two ways, standing or in recumbence. For small or medium sized ungulates, they bed to rest in most cases, and standing rest is very rare and hardly seen. Here we described a standing rest behaviour of medium sized Tibetan antelopes (Pantholops hodgsonii) living on the roof of the world, Tibet Plateau, which has not been reported before. We named the standing rest behaviour here as Puppet behaviour, since the antelope can stand still for a certain time just like a Puppet. Of the total 304 focal individuals, 48.3% (98/203) of adult and sub-adult males expressed the Puppet behaviour, whereas only 6.3% (6/96) of females did, indicating an obvious sexual difference. Puppet behaviour occurred more frequently at noon and in the afternoon on sunny and cloudy days, meaning that day time and weather were both influential factors. Puppet behaviour was usually accompanied with rumination and sometimes ended with leg-shaking. Our results suggest that Puppet behaviour is probably an adaptive form of rest, which serves a thermoregulatory and anti-predation function, and is much simpler and safer than recumbent rest.

animal behavior and cognition↗

bioRxiv2018

Convergent evolution of bird-mammal shared characteristics for adapting to nocturnality

The diapsid lineage (birds) and synapsid lineage (mammals), share a suite of functionally similar characteristics (e.g., endothermy) that are considered to be a result of their convergent evolution, but the candidate selections leading to this convergent evolution are still under debates. Here, we used a newly developed molecular phyloecological approach to reconstruct the diel activity pattern of the common ancestors of living birds. Our results strongly suggest that they had adaptations to nocturnality during their early evolution, which is remarkably similar to that of ancestral mammals. Given their similar adaptation to nocturnality, we propose that the shared traits in birds and mammals may have evolved as a result of the convergent evolution of their early ancestors adapting to ecological factors (e.g., low ambient temperature) associated with nocturnality. Finally, a conceptually unifying ecological model on the evolution of endothermy in diverse organisms with an emphasis on low ambient temperature is proposed. We reason that endothermy may evolve as an adaptive strategy to enable organisms to effectively implement various life cycle activities under relatively low-temperature environments. In particular, a habitat shift from high-temperature to relatively low-temperature environments is identified as a common factor underlying the evolution of endothermy.

evolutionary biology↗

bioRxiv2018

Molecular mimicry in deoxy-nucleotide catalysis: the structure of Escherichia coli dGTPase reveals the molecular basis of dGTP selectivity

Deoxynucleotide triphosphate triphosphyohydrolyases (dNTPases) play a critical role in cellular survival and DNA replication through the proper maintenance of cellular dNTP pools by hydrolyzing dNTPs into deoxynucleosides and inorganic triphosphate (PPPi). While the vast majority of these enzymes display broad activity towards canonical dNTPs, exemplified by Sterile Alpha Motif (SAM) and Histidine-aspartate (HD) domain-containing protein 1 (SAMHD1), which blocks reverse transcription of retroviruses in macrophages by maintaining dNTP pools at low levels, Escherichia coli (Ec)-dGTPase is the only known enzyme that specifically hydrolyzes dGTP. However, the mechanism behind dGTP selectivity is unclear. Here we present the free-, ligand (dGTP)- and inhibitor (GTP)-bound structures of hexameric E. coli dGTPase. To obtain these structures, we applied UV-fluorescence microscopy, video analysis and highly automated goniometer-based instrumentation to map and rapidly position individual crystals randomly-located on fixed target holders, resulting in the highest indexing-rates observed for a serial femtosecond crystallography (SFX) experiment. The structure features a highly dynamic active site where conformational changes are coupled to substrate (dGTP), but not inhibitor binding, since GTP locks dGTPase in its apo form. Moreover, despite no sequence homology, dGTPase and SAMHD1 share similar active site and HD motif architectures; however, dGTPase residues at the end of the substrate-binding pocket mimic Watson Crick interactions providing Guanine base specificity, while a 7 [A] cleft separates SAMHD1 residues from dNTP bases, abolishing nucleotide-type discrimination. Furthermore, the structures sheds light into the mechanism by which long distance binding (25 [A]) of single stranded DNA in an allosteric site primes the active site by conformationally \"opening\" a tyrosine gate allowing enhanced substrate binding.\n\nSignificance StatementdNTPases play a critical role in cellular survival through maintenance of cellular dNTP. While dNTPases display activity towards dNTPs, such as SAMHD1 -which blocks reverse transcription of HIV-1 in macrophages- Escherichia coli (Ec)-dGTPase is the only known enzyme that specifically hydrolyzes dGTP. Here we use novel free electron laser data collection to shed light into the mechanisms of (Ec)-dGTPase selectivity. The structure features a dynamic active site where conformational changes are coupled to dGTP binding. Moreover, despite no sequence homology between (Ec)-dGTPase and SAMHD1, both enzymes share similar active site architectures; however, dGTPase residues at the end of the substrate-binding pocket provide dGTP specificity, while a 7 [A] cleft separates SAMHD1 residues from dNTP.

biophysics↗

bioRxiv2018

Recent mixing of Vibrio parahaemolyticus populations

BackgroundHumans have profoundly affected the ocean environment but little is known about anthropogenic effects on the distribution of microbes. Vibrio parahaemolyticus is found in warm coastal waters and causes gastroenteritis in humans and economically significant disease in shrimps.\n\nResultsBased on data from 1,103 genomes, we show that V. parahaemolyticus is divided into four diverse populations, VppUS1, VppUS2, VppX and VppAsia. The first two are largely restricted to the US and Northern Europe, while the others are found worldwide, with VppAsia making up the great majority of isolates in the seas around Asia. Patterns of diversity within and between the populations are consistent with them having arisen by progressive divergence via genetic drift during geographical isolation. However, we find that there is substantial overlap in their current distribution. These observations can be reconciled without requiring genetic barriers to exchange between populations if dispersal between oceans has increased dramatically in the recent past. We found that VppAsia isolates from the US have an average of 1.01% more shared ancestry with VppUS1 and VppUS2 isolates than VppAsia isolates from Asia itself. Based on time calibrated trees of divergence within epidemic lineages, we estimate that recombination affects about 0.017% of the genome per year, implying that the genetic mixture has taken place within the last few decades.\n\nConclusionsThese results suggest that human activity, such as shipping and aquatic products trade, are responsible for the change of distribution pattern of this marine species.

microbiology↗

bioRxiv2018

Co-culture of soil biofilm isolates enables the discovery of novel antibiotics

Bacterial natural products (NPs) are considered to be a promising source of drug discovery. However, the biosynthesis gene clusters (BGCs) of NP are not often expressed, making it difficult to identify them. Recently, the study of biofilm community showed bacteria may gain competitive advantages by the secretion of antibiotics, implying a possible way to screen antibiotic by evaluating the social behavior of bacteria. In this study, we have described an efficient workflow for novel antibiotic discovery by employing the bacterial social interaction strategy with biofilm cultivation, co-culture, transcriptomic and genomic methods. We showed that a biofilm dominant species, i.e. Pseudomonas sp. G7, which was isolated from cultivated soil biofilm community, was highly competitive in four-species biofilm communities, as the synergistic combinations preferred to exclude this strain while the antagonistic combinations did not. Through the analysis of transcriptomic changes in four-species co-culture and the complete genome of Pseudomonas sp. G7, we finally discovered two novel non-ribosomal polypeptide synthetic (NRPS) BGCs, whose products were predicted to have seven and six amino acid components, respectively. Furthermore, we provide evidence showing that only when Pseudomonas sp. G7 was co-cultivated with at least two or three other bacterial species can these BGC genes be induced, suggesting that the co-culture of the soil biofilm isolates is critical to the discovery of novel antibiotics. As a conclusion, we set a model of applying microbial interaction to the discovery of new antibiotics.

microbiology↗

bioRxiv2018

In Vitro Activities of Daptomycin Combined with Fosfomycin or Rifampin on Planktonic and Adherent Linezolid-resistant Enterococcus faecalis

This study aimed to explore daptomycin combined with fosfomycin or rifampin against the planktonic and adherent linezolid-resistant isolates of Enterococcus faecalis. Four linezolid-resistant isolates of E. faecalis which formed biofilms were collected for this study. Biofilm biomasses were detected by crystal violet staining. The adherent cells in the mature biofilms were counted by CFU numbers and observed by confocal laser scanning microscope (CLSM). In time-killing studies, daptomycin combined with fosfomycin or rifampin (4xMIC) demonstrated bactericidal activities on the planktonic cells, and daptomycin combined with fosfomycin killed more planktonic cells (at least 2-log10 CFU/ml) than daptomycin or fosfomycin alone. Daptomycin alone showed activities against the mature biofilms, and daptomycin combined with fosfomycin (16xMIC) demonstrated significantly more activity than daptomycin or fosfomycin alone against the mature biofilms in three of the four isolates. Daptomycin alone effectively killed the adherent cells, and daptomycin combined with fosfomycin (16xMIC) killed more adherent cells than daptomycin or fosfomycin alone in these mature biofilms. The high concentrations of daptomycin (512 mg/L) combined with fosfomycin indicated more activity than 16xMIC of daptomycin combined with fosfomycin on the adherent cells and the mature biofilms. The addition of rifampin increased the activity of daptomycin against the biofilms and the adherent cells of FB-14 and FB-80 isolates, but was not observed in FB-1 and FB-2 isolates. In conclusion, daptomycin combined with fosfomycin works effectively against the planktonic and adherent linezolid-resistant isolates of E. faecalis. The role of rifampin in these linezolid-resistant isolates is discrepant and needs more studies.

microbiology↗

bioRxiv2018

Proteome and microbiota analysis reveals alterations of liver-gut axis under different stocking density of Peking ducks

The aim of this study was to determine the impact of stocking density on the liver proteome and cecal microbiota of Peking ducks. A total of 1,200 ducks with 21-day old were randomly allotted into 5 stocking density groups of 5, 6, 7, 8 and 9 ducks/m2, with 6 replicates for each group. At 40 days of age, duck serum and pectorals were collected for biochemical tests; liver and cecal contents of ducks were gathered for proteome and microbiota analysis, respectively. Serum MDA increased while pectorals T-AOC reduced linearly with enhancing stocking density. Duck lipid metabolism was altered under different stocking density as well. Serum LDL-C increased linearly with increasing stocking density. Proteome analysis revealed fatty acid biosynthesis proteins such as acyl-CoA synthetase family member 2 and fatty acid oxidation related proteins including acyl-CoA dehydrogenase long chain and acyl-coenzyme A oxidase were enriched in high stocking density group. Additionally, high stocking density increased oxidative response related proteins such as DDRGK domain containing 1 while diminished anti-oxidant capacity related proteins including regucalcin and catalase. 16S rDNA analysis revealed that higher stocking density was accompanied with decreased microbial diversity, as well as depletion of anti-inflammatory bacterial taxa, including Bacteroidales, Butyricimonas and Alistipe. In addition, decreased bile acid metabolism-associated bacteria such as Ruminococcaceae, Clostridiales and Desulfovibrionaceae were found in the high-density group. Both proteome and 16S rDNA results showed inflammation and chronic liver disease trend in the high-density group, which suggests the involvement of the liver-gut axis in oxidative stress.

microbiology↗

bioRxiv2018

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability

Can transcriptomic alterations drive the evolution of tumors? We rationalize that expressional changes found in all patients arise earlier in tumor development compared to alterations that occur only in limited subsets of patients. Our analyses of non-mutated genes from the non-amplified regions of the genome of 158 triple negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC. Phylogenetic analyses of these genes predict a \"punctuated burst\" of multiple gene up-regulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression. Remarkably, this punctuated burst of expressional changes is instigated by hypoxia-related molecular events, predominantly in two groups of genes that control chromosomal instability (CIN) and remodel tumor microenvironment (TME). We conclude that alterations in the transcriptome are not stochastic and that early stage hypoxia induces CIN and TME remodeling to permit further tumor evolution.

cancer biology↗

bioRxiv2018

UDP-glucose:anthocyanidin 3-O-glucoside-2”-O-glucosyltransferase catalyzes further glycosylation of anthocyanins in purple Ipomoea batatas

Glycosylation contributes to the diversity and stability of anthocyanins in plants. The process is catalyzed by various glucosyltransferases using different anthocyanidin aglycones and glycosyl donors. An anthocyanidin 3-O-glucoside-2\"-O-glucosyltransferase (3GGT) from purple sweetpotato (cv. Ayamurasaki) served for the catalytic conversion of anthocyanidin 3-O-glucoside into anthocyanidin 3-O-sophoroside, which is functionally different from the 3GGT ortholog of Arabidopsis. The phylogenetic analysis indicates regioselectivity of 3GGT using UDP-xylose or UDP-glucose as the glycosyl is divergent between Convolvulaceae and Arabidopsis. Homology-based protein modeling and site-directed mutagenesis of Ib3GGT and At3GGT suggested that the Thr-138 of Ib3GGT is a key amino acid residue for UDP-glucose recognition and plays a major role in sugar donor selectivity. The wild type and ugt79b1 mutants of Arabidopsis plants overexpressing Ib3GGT produced the new component cyanidin 3-O-sophoroside. Moreover, Ib3GGT expression was associated with anthocyanin accumulation in different tissues during Ayamurasaki plant development and was regulated by the transcription factor IbMYB1. The localization assay of Ib3GGT showed that further glycosylation occurs in the cytosol and not endoplasmic reticulum. The present study revealed the function of Ib3GGT in further glycosylation of anthocyanins and its Thr-138 is the key amino acid residue for UDP-glucose recognition.

plant biology↗

bioRxiv2018

Low frequency ultrasound enhances chemotherapy sensitivity and induces autophagy in human paclitaxel resistance prostate cancer PC-3R cells through the ERs-mediated PI3K/Akt/mTOR signaling pathway

Sonodynamic therapy (SDT) as an emerging tumor-assisting method has attracted a great deal of interest in tumor therapy research in recent years. However, autophagy has been observed in several cancer cells treated with SDT and its role and mechanism are not clear. In the present study, we have investigated the effect of low frequency ultrasound on paclitaxel(PTX) resistance prostate cancer PC-3R cells and demonstrated that low frequency ultrasound could induce cancer cell apoptosis, inhibit the expression of multiple drug resistance genes (MRP3, MRP7 and P-glycoprotein) and reverse drug resistance; we further found that low frequency ultrasound induced autophagy in PC-3R cells. Our results demonstrated that low frequency ultrasound enhanced chemotherapy sensitivity and induced autophagy in PC-3R cells by inhibiting the PI3K/AKT/mTOR pathway. Moreover, we observed that low frequency ultrasound-induced cell autophagy was correlated with endoplasmic reticulum stress (ERs). 4-phenylbutyric acid (4-PBA) - mediated protection against ERs clearly implicated ERs in the activation of autophagy and cell apoptosis. In addition, the results showed that ERs served as an upstream effector of the PI3K/AKT/mTOR pathway. More importantly, we observed that inhibition of low frequency ultrasound-induced autophagy enhanced ERs and improved the role of low frequency ultrasound in reversing drug resistance. Over all, our findings provide new insights into the molecular mechanisms underlying low frequency ultrasound-mediated reversal of drug resistance and autophagy in PC-3R cells and support autophagy as a potential agent for enhancing anti-cancer effect of SDT.

cancer biology↗

bioRxiv2018

High-throughput identification and marker development of perfect SSR for cultivated genus of passion fruit (Passiflora edulis)

Simple sequence repeat (SSR) markers are characterized by high polymorphism, good reproducibility and co-dominance etc. They can be easily applied to develop efficient, simple and practical molecular markers. In the present study, bioinformatics methods were applied to identify high-throughput perfect SSRs of cultivar Passiflora genome. A total of 13104 perfect SSRs were obtained. SSR core sequence structure is mainly 2-4 bases, the maximum numbers are TA, AT, TC and AG. The maximum numbers of repetitions were up to 20 times. A total of 12934 pairs of SSR markers were developed by using bioinformatics software, and 20 pairs of markers were selected for amplification specificity assessment of MTX and WJ10, and the polymorphism rate was as high as 60%. The large-scale development of the SSR markers of Passiflora cultivar has paved a foundation for the efficient utilization of the germplasm resources of passion fruit, genetic improvement of the varieties and molecular breeding.

genomics↗

bioRxiv2018

Post-reactivation new learning impairs and updates human episodic memory through dissociable processes

Learning of competing information after reactivation has the potential to disrupt memory reconsolidation and thus impair a consolidated memory. Yet this effect has rarely been detected in episodic memory. By introducing an additional retrieving cue to the target memory, the current study detected significant impairment on the reactivated episodic memory, in addition to an integration of new information to the old memory. However, while the integration effect followed the time window of reconsolidation disruption, the impairment effect did not. MEG measurements further revealed alpha power change during reactivation and post-reactivation learning which showed different correlation patterns with the integration and impairment effects, confirming that the two effects relied on different processes. Therefore, post-reactivation new learning disrupts episodic memory but not through reconsolidation disruption. Further findings that the impairment effect was correlated with participants voluntary inhibition ability suggest an inhibition-based memory updating process underlying post-reactivation new learning.

neuroscience↗

bioRxiv2018

Inferring the ancestry of parents and grandparents from genetic data

Inference of admixture proportions is a classical statistical problem in population genetics. Standard methods implicitly assume that both parents of an individual have the same admixture fraction. However, this is rarely the case in real data. In this paper we show that the distribution of admixture tract lengths in a genome contains information about the admixture proportions of the ancestors of an individual. We develop a Hidden Markov Model (HMM) framework for estimating the admixture proportions of the immediate ancestors of an individual, i.e. a type of decomposition of an individuals admixture proportions into further subsets of ancestral proportions in the ancestors. Based on a genealogical model for admixture tracts, we develop an efficient algorithm for computing the sampling probability of the genome from a single individual, as a function of the admixture proportions of the ancestors of this individual. This allows us to perform probabilistic inference of admixture proportions of ancestors only using the genome of an extant individual. We perform extensive simulations to quantify the error in the estimation of ancestral admixture proportions under various conditions. To illustrate the utility of the method, we apply it to real genetic data. Author summaryAncestry inference is an important problem in genetics and is used commercially by a number of companies affecting millions of consumers of genetic ancestry tests. In this paper, we show that it is possible, not only to estimate the ancestry fractions of an individual, but also, with some uncertainty, to estimate the ancestry fractions of an individuals ancestors. For example, if an individual traces his/her ancestry 50% to Asia and 50% to Europe, it is possible to distinguish between the individual having two parents that each are 50:50 composites of Asian and European ancestry, or one parent from Asia and one from Europe. It is likewise also possible to make inferences about grandparents. We present a computationally efficient method for making such inferences called PedMix. PedMix is based on a probabilistic model for the descendant and the recent ancestors. PedMix infers admixture proportions of recent ancestors (parents, grandparents or even great grandparents) using whole-genome genetic variation data from a focal individual. Results on both simulated and real data show that PedMix performs reasonably well in most scenarios.

genetics↗

bioRxiv2018

A scalable estimator of SNP heritability for Biobank-scale data

MotivationHeritability, the proportion of variation in a trait that can be explained by genetic variation, is an important parameter in efforts to understand the genetic architecture of complex phenotypes as well as in the design and interpretation of genome-wide association studies. Attempts to understand the heritability of complex phenotypes attributable to genome-wide SNP variation data has motivated the analysis of large datasets as well as the development of sophisticated tools to estimate heritability in these datasets.\n\nLinear Mixed Models (LMMs) have emerged as a key tool for heritability estimation where the parameters of the LMMs, i.e., the variance components, are related to the heritability attributable to the SNPs analyzed. Likelihood-based inference in LMMs, however, poses serious computational burdens.\n\nResultsWe propose a scalable randomized algorithm for estimating variance components in LMMs. Our method is based on a MoM estimator that has a runtime complexity [Formula] for N individuals and M SNPs (where B is a parameter that controls the number of random matrix-vector multiplications). Further, by leveraging the structure of the genotype matrix, we can reduce the time complexity to [Formula].\n\nWe demonstrate the scalability and accuracy of our method on simulated as well as on empirical data. On standard hardware, our method computes heritability on a dataset of 500, 000 individuals and 100, 000 SNPs in 38 minutes.\n\nAvailabilityThe RHE-reg software is made freely available to the research community at: https://github.com/sriramlab/RHE-reg\n\nContactsriram@cs.ucla.edu

bioinformatics↗