Biology subjects

Sun, Q.

Publications and source records attributed to Sun, Q..

At least 145 records · Page 8Linked to original sources

bioRxiv2022

openNAU: An open-source platform for normalizing, analyzing, and visualizing untargeted metabolomics data

MotivationAs an important part of metabolomics analysis, untargeted metabolomics has become a powerful tool in the study of tumor mechanisms and the discovery of metabolic markers with high-throughput spectrometric data which also brings great challenges to data analysis from the extraction of raw data to the identification of differential metabolites. To date, a large number of analytical tools and processes have been developed and constructed to serve untargeted metabolomics research. The different selection of analytical tools and parameter settings lead to varied results of untargeted metabolomics data. Our goal is to establish an easily operated platform and obtain a repeatable analysis result. ResultsWe used the R language basic environment to construct the preprocessing system of the original data and the LAMP (Linux + Apache + MySQL + PHP) architecture to build a cloud mass spectrum data analysis system. An open-source analysis software for untargeted metabolomics data (openNAU) was constructed. It includes the extraction of raw mass data and quality control for the identification of differential metabolic ion peaks. A reference metabolomics database based on public databases was also constructed. Finally, a complete analysis system platform for untargeted metabolomics was established. This platform provides a complete template interface for the addition and updating of the analysis process, so we can finish complex analyses of untargeted metabolomics with simple human-computer interactions. Availability and ImplementationThe source code can be downloaded from https://github.com/zjuRong/openNAU. Contactsunqingrong@zju.edu.cn

bioinformatics↗

bioRxiv2022

Target sequence capture data shed light on the deeper evolutionary relationship on the subgenus Chamaecerasus of Lonicera (Caprifoliaceae)

The genus Lonicera L. is widely distributed and is well-known for its high species richness and morphological diversity. Previous studies have suggested that many sections of Lonicera are not monophyletic and phylogenetic relationships within the genus are still poorly known. In this study, we sampled 37 accessions of Lonicera, covering four sections of subgenus Chamaecerasus plus six outgroup taxa to recover the main clades of Lonicera based on sequences of nuclear loci generated by target enrichment and cpDNA from genome skimming. We found extensive cytonuclear discordance across the subgenus. Both nuclear and plastid phylogenetic analyses supported subgenus Chamaecerasus sister to subgenus Lonicera. Within subgenus Chamaecerasus, sections Isika and Niatoon were polyphyletic. Based on the nuclear and chloroplast phylogenies we propose to merge Lonicera korolkowii into section Coeloxylosteum and Lonicera caerulea into section Nintooa. In addition, Lonicera is estimated to have originated in the late Miocene (19.84 Ma). The stem age of section Nintooa was estimated to be 17.97 Ma (95% HPD: 13.31- 22.89). The stem age of subgenus Lonicera was estimated to be 16.35 Ma (95% HPD: 9.33- 45.15). Ancestral area reconstruction analyses indicate that Lonicera originated in the Qinghai Tibet Plateau (QTP) and Asia, with subsequent dispersal into other areas. The aridification of the Asian interior possibly promoted the rapid radiation of Lonicera within this region, and the uplift of the QTP appears to have triggered the dispersal and recent rapid diversification of the genus in the QTP and adjacent regions. Overall, this study provides new insights into the taxonomically complex lineages of Lonicera at the section level and the process of speciation.

evolutionary biology↗

bioRxiv2022

Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export

Skeletal muscle stem cells (also known as satellite cells, SCs) are essential for muscle regeneration and the regenerative activities of SCs are intrinsically governed by gene regulatory mechanisms but the post-transcriptional regulation in SCs remains largely unknown. N(6)-methyladenosine (m6A) modification of RNAs is the most pervasive and highly conserved RNA modification in eukaryotic cells and exerts powerful impact on almost all aspects of mRNA processing which is mainly endowed by its binding with m6A reader proteins. Here in this study, we investigate the previously uncharacterized regulatory roles of YTHDC1, a m6A reader in SCs. Our results demonstrate YTHDC1 is an essential regulator of SC activation and proliferation upon acute injury induced muscle regeneration. The induction of YTHDC1 is indispensable for SC activation and proliferation thus inducible YTHDC1 depletion almost abolishes SC regenerative capacity. Mechanistically, transcriptome-wide profiling using LACE-seq in both SCs and C2C12 myoblasts identifies m6A mediated binding targets of YTHDC1. Next, splicing analysis defines splicing mRNA targets of m6A-YTHDC1. Furthermore, nuclear export analysis also leads to identification of potential mRNA export targets of m6A-YTHDC1 in SCs and C2C12 myoblasts and interestingly some mRNAs can be regulated at both splicing and export levels. Lastly, we map YTHDC1 interacting protein partners in myoblasts and unveil a myriad of factors governing mRNA splicing, nuclear export and transcription, among which hnRNPG appears to be a bona fide interacting partner of YTHDC1. Altogether, our findings uncover YTHDC1 as an essential factor controlling SC regenerative ability through multi-faceted gene regulatory mechanisms in myoblast cells.

molecular biology↗

bioRxiv2022

Obesity promotes breast epithelium DNA damage in BRCA mutation carriers

Obesity is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated bodyweight is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear due to inconsistent findings from epidemiological studies and lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelium of BRCA mutation carriers is positively correlated with body mass index and with biomarkers of metabolic dysfunction. Additionally, RNA-sequencing reveals significant obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which impacts neighboring breast epithelial cells. We found that blockade of estrogen biosynthesis or estrogen receptor activity decreases DNA damage, whereas treatment with leptin or insulin increases DNA damage in BRCA heterozygous epithelial cells. Furthermore, we show that increased adiposity is associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1+/- mice. Overall, our results provide mechanistic evidence in support of a link between bodyweight and breast cancer development in BRCA mutation carriers and suggests that maintaining a healthy bodyweight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population. One Sentence SummaryElevated bodyweight is positively associated with DNA damage in breast epithelium of BRCA mutation carriers

cancer biology↗

bioRxiv2022

Rho of plant GTPase MxROP1 regulates Fe deficiency responses by targeting Zinc Ribbon 3 in apple rootstock

Small G protein is a multifunctional molecular switch that can regulate plant growth, development and responses to the environment. However, how Rho-related GTPase of plants (ROPs) regulates the response to Fe deficiency has not been well clarified. Here, we found that Fe deficiency induced MxROP1 in Malus xiaojinensis at both the transcriptional and translational levels. The overexpression of MxROP1, MxROP1DN (inactive form) and MxROP1CA (active form) in apple roots increased the activity of ferric chelate reductase and the ability to acidify the rhizosphere, and lines that overexpressed MxROP1DN exhibited the strongest reaction to enhance Fe uptake. Yeast two-hybrid library screening indicated that MxROP1 interacted with ZR3.1, a DNL zinc finger protein that negatively regulates Fe deficiency responses. We further identified their interaction in vitro and in vivo using pull-down and bimolecular fluorescence complementation assays, respectively, and MxROP1DN-MxZR3.1 interacted the most strongly. Furthermore, MxROP1 negatively affected the stability of MxZR3.1 protein in vitro as shown by a cell semi-degradation assay, and the application of MG132 inhibited the degradation of MxZR3.1-HIS proteins. This indicated that MxROP1 caused the degradation of MxZR3.1 protein through the 26S proteasome pathway. Similar results were found in OE-MxROP1+OE-MxZR3.1 transgenic apple callus compared with those in the OE-MxZR3.1 callus. We also demonstrated that MxZR3.1 interacted with MxbHLH39, a known positive transcription factor and core component of Fe deficiency, and MxROP1 affected the interaction of MxZR3.1-MxbHLH39 using a competitive binding assay. This illuminated one MxROP1-MxZR3.1-MxbHLH39 pathway that maintains Fe homeostasis in M. xiaojinensis.

plant biology↗

bioRxiv2022

Machine learning reveals conserved chromatin patterns determining meiotic recombination sites in plants

Distribution of meiotic recombination events in plants has been associated with local chromatin and DNA characteristics, chromosome landmark proximity, and other features1-7. However, relative importance of these characteristics is unclear and it is unknown if they are sufficient to unambiguously determine recombination landscape8. Here, we analyzed over 40 DNA sequence, chromatin, and chromosome location features of maize and Arabidopsis recombination sites using machine learning9,10. We discovered that a combination of just three features, CG methylation, CHG methylation, and nucleosome occupancy, enabled identification of exact crossover site with 90% accuracy. These results imply redundancy of most recombination site characteristics. Recombination takes place in a small fraction of the genome with chromatin features distinct from those of genome at large. Surprisingly, crossover sites show elevated heterochromatin histone marks despite low DNA methylation. Crossover site features show broad evolutionary conservation, which will enable creating genetic maps in species where conventional mapping is unfeasible.

plant biology↗

bioRxiv2022

Sex differences in the nasal microbiome of healthy young adults

Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections (RTIs) between males and females. It is recently hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities, but without evidence. In this work, we study the nasal microbiome of healthy young adults in, as of today, the largest cohort based on deep shot-gun metagenomic sequencing. We mainly focus on the bacteriome, but also integrate the mycobiome to get a more holistic perspective. De novo assembly is performed to catalog the nasal bacterial colonizers/residents, which also identify and therefore account for uncharacterized components of the community. The bacteriome is then profiled based on the non-redundant metagenome-assembled genomes (MAGs) catalog constructed therefrom. Unsupervised clustering reveals clearly separable structural patterns in the nasal microbiome between the two sexes. Following this link, we systematically evaluate sex differences for the first time and reveal extensive sex-specific features in the nasal microbiome composition. More importantly, through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the nasal microbiome of females than that of males. The analysis of the keystone bacteria of the communities reveal that the sex-dependent evolutionary characteristics might have contributed to this difference. HighlightsThe non-redundant nasal bacterial MAGs catalog constructed from ultra-deeply sequenced metagenomic data provides a valuable resource. Integrating nasal bacteriome and mycobiome data provides a more holistic perspective for the understudied human nasal microbiome. Unsupervised clustering helps uncover extensive sex differences in the nasal microbiome compositions. Network analyses capture markedly higher ecological stability and antagonistic potentials in the nasal microbiome of females than that of males. Sex-dependent genetic evolutionary forces play a role in the shaping of keystones in the nasal microbial community.

microbiology↗

bioRxiv2022

Molecular Aggregation Induced Photoacoustics for NIR-II in vivo Imaging

Molecular aggregation induced photo-properties alteration has been found to play a crucial role in the light induced processes, such as aggregation induced emission (AIE) and J aggregation induced dramatic absorption red shift. The light induced acoustic process (photoacoustic) is also considered to be one of the most essential characters of the light absorbing molecules. However, to the best of our knowledge, the molecular aggregation induced photoacoustic effect (MAIPA) has never been reported. Herein, we report the first MAIPA effect for which the PA intensity is dominated by the molecular aggregation, rather than by absorbance as usual concerned. Molecular aggregation induces a strong electronic coupling effect, resulting in significant absorption suppression from the individual state to highly aggregated state (around 5 molecules aggregated). However, the corresponding PA efficiency was found to be about 2-orders of magnitude greater for the latter. A well-behaved linear correlation between the molecular aggregation level and MAIPA effect was observed. The surprisingly significant MAIPA effect was realized via novel NIR-II squaraine-benzothiopyrylium dyes. Excellent photophysical properties of the novel NIR-II dyes were achieved, such as large absorption extinction coefficient and high photostability. Thanks to the relatively narrow FWHM and the high PA efficiency of SQN2@PMAOPEG and ZC825@BSA, in vivo multiplex PA imaging was demonstrated for tumor tissue and macrophage cells, blood and lymphoid vessels.

biochemistry↗

bioRxiv2022

Cryo-EM Structure of R-loop monoclonal antibody S9.6 in recognizing RNA:DNA hybrids

The three-stranded chromatin structure R-loop is commonly found in the genomes of different species, and functions as the double-edged sword in gene expression and genome stability. The monoclonal antibody S9.6 specifically recognizes RNA:DNA hybrids, and has been widely used as a powerful tool to detect R-loops genome-widely. However, the structure basis and the molecular recognition mechanism of S9.6 to the nucleic acid substrates is still limited. Here, applying cryo-electron microscopy, we have determined a 4.9 [A] structure of S9.6 antigen-binding fragment (Fab) complexed with RNA:DNA hybrids. We found that the native Fab cleaved from S9.6 antibody has much higher affinity to RNA:DNA hybrids than to the double-strand RNAs, and the minimum length of the hybrids should be more than 8 base-pair. The structure of Fab binding to the hybrids suggested one loop of S9.6 heavy chain inserts into the minor groove in the RNA:DNA hybrids, and the other three loops flank to the hybrids. The top of four loop all enrich with aromatic or positive charge residues which are potentially responsible for nucleic acids binding specificity. Our results revealed the recognition mechanism of S9.6 on R-loops, which directs the future engineering of S9.6, and thus could further promote R-loop biology studies.

molecular biology↗

bioRxiv2022

Downregulation of Stem-loop binding protein by nicotine via α7-nicotinic acetylcholine receptor and its role in nicotine-induced cell transformation

The use of electronic-cigarettes (e-cigs) has increased substantially in recent years, particularly among the younger generations. Liquid nicotine is the main component of e-cigs. Previous studies have shown that mice exposed to e-cig aerosols developed lung adenocarcinoma and bladder hyperplasia. These findings implicated a potential role for e-cig aerosols and nicotine in cancer development, although the underlying mechanisms are not fully understood. Here we report that exposure to liquid nicotine or nicotine aerosol generated from e-cig induces downregulation of Stem-loop binding protein (SLBP) and polyadenylation of canonical histone mRNAs in human bronchial epithelial cells and in mice lungs. Canonical histone mRNAs typically do not end in a poly(A) tail and the acquisition of such a tail via depletion of SLBP has been shown to causes chromosome instability. We show that nicotine-induced SLBP depletion is reversed by an inhibitor of 7-nAChR (nicotinic acetylcholine receptors) or siRNA specific for 7-nAChR, indicating a nAChR-dependent reduction of SLBP by nicotine. Moreover, not only CDK1 and CK2, two kinases well known for their function for SLBP phosphorylation and degradation, but also CDK2 and PI3K/AKT pathways are shown to be involved, 7-nAChR-dependently, in nicotine-induced SLBP depletion. Importantly, nicotine-induced anchorage-independent cell growth is attenuated by inhibition of 7-nAChR and is rescued by overexpression of SLBP. We propose that the SLBP depletion and polyadenylation of canonical histone mRNAs via activation of 7-nAChR and a series of downstream signal transduction pathways, are critical for nicotine-induced cell transformation and potential carcinogenesis.

molecular biology↗

bioRxiv2022

Thyroid hormone induces B cells abnormal differentiation via overexpression of B cell-activating factor

Breakdown of tolerance and abnormal activation in B cells is an important mechanism in Graves disease (GD) pathogenesis. However, the mechanism by which B cells are abnormal differentiated and activated in GD remains elusive. Here, we show that elevated BAFF expression is positively correlated with serum thyroid hormone (TH) levels in GD patients and high TH levels can induce BAFF overexpression and lead to the abnormal differentiation of B cells in mice. This BAFF overexpression can be seen in many tissues. In the spleens of mice, high TH levels induce M1 macrophages polarization, which generates BAFF overexpression. Our findings open a new perspective on the interactions between endocrine and immune system and provide insight into the involvement of thyroid hormones in the development and progression of GD.

immunology↗

bioRxiv2022

SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing

Alternative splicing expands the transcriptome and proteome complexity and plays essential roles in tissue development and human diseases. However, how alternative splicing regulates spermatogenesis remains largely unknown. Here, using germ cell-specific knockout mouse model, we demonstrated that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. Depletion of Srsf10 in germ cells had little effect on the formation of SSCs but impeded the expansion of progenitor spermatogonia, leading to the failure of spermatogonia differentiation and meiosis initiation. This was further evidenced by the decreased expression of progenitor cell markers in bulk RNA-seq, and much less progenitor and differentiating spermatogonia in single-cell RNA-seq data. Furthermore, the expression of genes involved in cell cycle was abnormal in all subtypes of spermatogonia identified in single-cell RNA-seq data. Notably, using isolated spermatogonia, we found that Srsf10 depletion disturbed the alternative splicing of hundreds of genes, which were preferentially associated with cell cycle, mitotic cell cycle checkpoint and germ cell development, including Dazl, Kit, Ret, Sycp1, Nasp and Bora. These data suggest that SRSF10 is critical for the expansion of progenitor spermatogonia by regulating alternative splicing, expanding our understanding of the mechanism underlying spermatogenesis.

developmental biology↗

bioRxiv2022

Near Infrared-II Fluorescent protein for In-vivo Imaging

In vivo fluorescent imaging in the second near-infrared window (NIR-II) provides an excellent approach for understanding the biological processes in substantially scattered tissue environments with reasonable temporal-spatial resolution. In spite of an enormous amount of organic and inorganic NIR-II fluorophores developed, there is no NIR-II fluorescent protein reported. Here, we present the first NIR-II fluorescent protein, IRFP1032 which exhibits strong exciton absorption and emission in the NIR-II region, with exciton extinction coefficient about 4.1 x106 M-1cm-1 at the excitation maximum 1008 nm, emission maximum of 1032 nm, and emission quantum yield about 0.84%. The IRFP1032 is found to be the brightest NIR-II fluorophore ever reported (brightness of 3.4 x 104 M-1cm-1 in PBS) which is thousands-fold brighter than IR26 in DCM. Taking the advantage of the excellent photo-properties of the NIR-II fluorescent proteins, a collection of high-quality in vivo imaging research was realized, for instance, real time observation of blood flow dynamics, dual-channel imaging of the lymphatic/blood vessel network and the trajectories of single bacterial cell travelling in blood vessels. Moreover, a mammalian expression vector was constructed for the IRFP1032, and the corresponding NIR-II fluorescence was able to be recorded unambiguously. The promising NIR-II in vivo imaging properties of IRPF1032 demonstrated here would open a new scene in fluorescent protein-based imaging.

biochemistry↗

bioRxiv2021

Leveraging TOPMed Imputation Server and Constructing a Cohort-Specific Imputation Reference Panel to Enhance Genotype Imputation among Cystic Fibrosis Patients

Cystic fibrosis (CF) is a severe genetic disorder that can cause multiple comorbidities affecting the lungs, the pancreas, the luminal digestive system and beyond. In our previous genome-wide association studies (GWAS), we genotyped [~]8,000 CF samples using a mixture of different genotyping platforms. More recently, the Cystic Fibrosis Genome Project (CFGP) performed deep ([~]30x) whole genome sequencing (WGS) of 5,095 samples to better understand the genetic mechanisms underlying clinical heterogeneity among CF patients. For mixtures of GWAS array and WGS data, genotype imputation has proven effective in increasing effective sample size. Therefore, we first performed imputation for the [~]8,000 CF samples with GWAS array genotype using the TOPMed freeze 8 reference panel. Our results demonstrate that TOPMed can provide high-quality imputation for CF patients, boosting genomic coverage from [~]0.3 - 4.2 million genotyped markers to [~]11 - 43 million well-imputed markers, and significantly improving Polygenic Risk Score (PRS) prediction accuracy. Furthermore, we built a CF-specific CFGP reference panel based on WGS data of CF patients. We demonstrate that despite having [~]3% the sample size of TOPMed, our CFGP reference panel can still outperform TOPMed when imputing some CF disease-causing variants, likely due to allele and haplotype differences between CF patients and general populations. We anticipate our imputed data for 4,656 samples without WGS data will benefit our subsequent genetic association studies, and the CFGP reference panel built from CF WGS samples will benefit other investigators studying CF.

genetics↗

bioRxiv2021

Alkaliphilus flagellata sp. nov., Butyricicoccus intestinisimiae sp. nov., Clostridium mobile sp. nov., Clostridium simiarum sp. nov., Dysosmobacter acutus sp. nov., Paenibacillus brevis sp. nov., Peptoniphilus ovalis sp. nov., and Tissierella simiarum sp. nov., isolated from monkey feces

Non-human primates harbor diverse microbiomes in their guts. As a part of China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (Macaca fascicularis). In this report, we communicate the characterization and taxonomy of 8 bacterial strains that were obtained from fecal samples of captive cynomolgus monkeys. The results revealed that they represented 8 novel bacterial species. The proposed names of the 8 novel species are Alkaliphilus flagellate (type strain MSJ-5T =CGMCC 1.45007T=KCTC 15974T), Butyricicoccus intestinisimiae MSJd-7T (type strain MSJd-7T =CGMCC 1.45013T =KCTC 25112T), Clostridium mobile (type strain MSJ-11T =CGMCC 1.45009T=KCTC 25065T), Clostridium simiarum (type strain MSJ-4T =CGMCC 1.45006T =KCTC 15975T), Dysosmobacter acutus (type strain MSJ-2T =CGMCC 1.32896T=KCTC 15976T), Paenibacillus brevis MSJ-6T (type strain MSJ-6T =CGMCC 1.45008T=KCTC 15973T), Peptoniphilus ovalis (type strain MSJ-1T =CGMCC 1.31770T=KCTC 15977T), and Tissierella simiarum (type strain MSJ-40T =CGMCC 1.45012T=KCTC 25071T).

microbiology↗

bioRxiv2021

Domestication Reshaped the Genetic Basis of Inbreeding Depression in a Maize Landrace Compared to its Wild Relative, Teosinte

Inbreeding depression is the reduction in fitness and vigor resulting from mating of close relatives observed in many plant and animal species. The extent to which the genetic load of mutations contributing to inbreeding depression is due to rare large-effect variation versus potentially more common variants with very small individual effects is unknown and may be affected by population history. We compared the effects of outcrossing and self-fertilization on 18 traits in a landrace population of maize, which underwent a population bottleneck during domestication, and a neighboring population of its wild relative teosinte. Inbreeding depression was greater in maize than teosinte for 15 of 18 traits, congruent with the greater segregating genetic load predicted from sequence data in the maize population. For many traits - and more commonly in maize - genetic variation among selffertilized families was less than expected based on additive and dominance variance estimated in outcrossed families, suggesting that a negative covariance between additive and homozygous dominance effects limits the variation available to selection under partial inbreeding. We identified quantitative trait loci (QTL) representing large-effect rare variants carried by only a single parent, which were more important in teosinte than maize. Teosinte also carried more putative juvenile-acting lethal variants identified by segregation distortion. These results suggest a mixture of mostly polygenic, smalleffect recessive variation underlying inbreeding depression, with an additional contribution from rare larger-effect variants that was more important in teosinte but depleted in maize following to the domestication bottleneck. Purging associated with the maize domestication bottleneck may have selected against large effect variants, but polygenic load is harder to purge and segregating mutational burden increased in maize compared to teosinte.

evolutionary biology↗

bioRxiv2021

Recurrent micropollutant exposure leads to divergent degradation abilities and community succession in a freshwater microbiome

The increasing-volume release of micropollutants into natural surface waters has raised great concern due to their environmental accumulation. Persisting micropollutants can impact multiple generations of organisms, but their microbially-mediated degradation and their influence on community assembly remain understudied. Here, freshwater microbes were treated with several common micropollutants, alone or in combination, and then transferred every 5 days to fresh medium containing the same micropollutants to mimic the repeated exposure of microbes. Metabarcoding of 16S rRNA gene makers was chosen to study the succession of bacterial assemblages following micropollutant exposure. The removal rates of micropollutants were then measured to assess degradation capacity of the associated communities. The degradation of micropollutants did not accelerate over time but altered the microbial community composition. Community assembly was dominated by stochastic processes during early exposure, via random community changes and emergence of seedbanks, and deterministic processes later in the exposure, via advanced community succession. Early exposure stages were characterized by the presence of sensitive microorganisms such as Actinobacteria and Planctomycetes, which were then replaced by more tolerant bacteria such as Bacteroidetes and Gammaproteobacteria. Our findings have important implication for ecological feedback between microbe-micropollutants under anthropogenic climate change scenarios.

ecology↗

bioRxiv2021

AFA: Computationally efficient Ancestral Frequency estimation in Admixed populations: the Hispanic Community Health Study/Study of Latinos

We developed a computationally efficient method, Ancestral Frequency estimation in Admixed populations (AFA), to estimate the frequencies of bi-allelic variants in admixed populations with an unlimited number of ancestries. AFA uses maximum likelihood estimation by modeling the conditional probability of having an allele given proportions of genetic ancestries. It can be applied using either global or local proportions of genetic ancestries. Simulations mimicking admixture demonstrated the high accuracy of the method. We implemented the method on data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an admixed population with three predominant continental ancestries: Amerindian, European, and African. Comparison of the European and African estimated frequencies to the respective gnomAD frequencies demonstrated high correlations, with Pearson R2=0.97-0.99. We provide a genome-wide dataset of the estimated three ancestral allele frequencies in HCHS/SOL for all available variants with allele frequency between 5%-95% in at least one of the three ancestral populations.

genomics↗