Characterization of nuclear mitochondrial insertions in the whole genomes of primates

Altres ajuts: CERCA Programme/Generalitat de Catalunya i Obra Social "La Caixa"The transfer and integration of whole and partial mitochondrial genomes into the nuclear genomes of eukaryotes is an ongoing process that has facilitated the transfer of genes and contributed to the evolution of various cellular pathways. Many previous studies have explored the impact of these insertions, referred to as NumtS, but have focused primarily on older events that have become fixed and are therefore present in all individual genomes for a given species. We previously developed an approach to identify novel Numt polymorphisms from next-generation sequence data and applied it to thousands of human genomes. Here, we extend this analysis to 79 individuals of other great ape species including chimpanzee, bonobo, gorilla, orang-utan and also an old world monkey, macaque. We show that recent Numt insertions are prevalent in each species though at different apparent rates, with chimpanzees exhibiting a significant increase in both polymorphic and fixed Numt sequences as compared to other great apes. We further assessed positional effects in each species in terms of evolutionary time and rate of insertion and identified putative hotspots on chromosome 5 for Numt integration, providing insight into both recent polymorphic and older fixed reference NumtS in great apes in comparison to human events

A mosquito small RNA genomics resource reveals dynamic evolution and host responses to viruses and transposons

Although mosquitoes are major transmission vectors for pathogenic arboviruses, viral infection has little impact on mosquito health. This immunity is due in part to mosquito RNA interference (RNAi) pathways that generate antiviral small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). RNAi also maintains genome integrity by potently repressing mosquito transposon activity in the germline and soma. However, viral and transposon small RNA regulatory pathways have not been systematically examined together in mosquitoes. Therefore, we developed an integrated Mosquito Small RNA Genomics (MSRG) resource that analyzes the transposon and virus small RNA profiles in mosquito cell cultures and somatic and gonadal tissues across four medically important mosquito species. Our resource captures both somatic and gonadal small RNA expression profiles within mosquito cell cultures, and we report the evolutionary dynamics of a novel Mosquito-Conserved piRNA Cluster Locus (MCpiRCL) composed of satellite DNA repeats. In the larger culicine mosquito genomes we detected highly regular periodicity in piRNA biogenesis patterns coinciding with the expansion of Piwi pathway genes. Finally, our resource enables detection of crosstalk between piRNA and siRNA populations in mosquito cells during a response to virus infection. The MSRG resource will aid efforts to dissect and combat the capacity of mosquitoes to tolerate and spread arboviruses

An integrated map of structural variation in 2,504 human genomes

© 2015 Macmillan Publishers Limited. All rights reserved. Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association

Data Management tools For Metagenomic Datasets, A Case Study: Characterization and Dysbiosis of Gut Microbiota In Apcmin/+ Mice With and Without Colon Tumors

Microorganism\u27s makeup half of earth\u27s biomass and are known to be the largest reservoir of biodiversity and genetic potential. They play an important role in maintaining equilibrium in the environment by taking part in several biogeochemical cycles. Microbes are found in every habitat, irrespective of the environmental factors. In human body microbes outnumber human cells by a factor of ten to one. Though their influence is not entirely known, it is probable that microbes play a major role in several metabolic processes. The gastrointestinal (GI) microbiota is the most abundant and diverse microbial community of human body. Several studies have shown that alteration in GI microbiota is associated with obesity, Inflammatory Bowel Disease (IBD), Crohn\u27s disease and even colorectal cancer. Colorectal cancers are the second leading cause of death in the US and it\u27s mainly due to the lack of early detection. If diagnosed at the polyp stage, they can be treated to avert progression of the cancer. But invasive and expensive detection procedures such as CT-colonoscopy and endoscopy make early screening inconvenient and difficult. Therefore, alternate diagnostic strategies such as finding possible biomarkers can help discover colon cancer at an early stage. So far, only 1-15% of microbes have been studied, due to the lack of ability to readily culture them. Past few decades have witnessed remarkable advancement in the field of microbiology since researchers started venturing in the `omics\u27 methods of investigation. These new-era of approaches such as metagenomics have created a paradigm shift in our understanding of microbial community structure and function. Metagenomics bypasses the need to culture the microbes and hence is a powerful tool to investigate microbial community in their natural environment. The advancements in sequencing technology such as high-throughput sequencing have made it possible to take full advantage of metagenomics. This has aided researcher to tap into greater depths of microbial diversity and changed our view of their relationship with other organisms. Although, the use of the next generation sequencing, results in large amounts of data that can get challenging while processing and analyzing. Hence, flexible and efficient data management pipelines that can be tailored to the needs of an individual research group are essential. The current data management pipeline was designed for processing, analyzing and storing metagenomic sequences obtained from 454-pyrosequencing technology. The data management pipeline was optimized using microbial metagenomes isolated from colon tissue and stool samples of APCmin/+ mice (a mouse model of colon cancer). A total of 171,405 unprocessed sequences were generated from proximal and distal colon sections as well as stool samples using 454-pyrosequencing. The preprocessing step resulted in 72% of high-quality reads that were used for further analyses. These high-quality sequences were then classified by aligning them against the Ribosomal Database Project (RDP) database. The relative abundance of each classified sequence was compared across samples to identify differences between the microbial communities contained in tumor versus non-tumor mice. It was observed that the proximal region showed higher variation compared to other samples. Also Prevotella was found in higher abundance in both tissue and stool samples of mice that developed tumors. Finally the clean and formatted reads were stored in a relational database management system that was created using `MySQL\u27. This database not only contains sequence information such as read length, average quality score and GC content, but also other related information such as, metadata, habitat and sequence annotation. A user interface was created using `PHP\u27 for data retrieval and sharing

Characterization of nuclear mitochondrial insertions in the whole genomes of primates

The transfer and integration of whole and partial mitochondrial genomes into the nuclear genomes of eukaryotes is an ongoing process that has facilitated the transfer of genes and contributed to the evolution of various cellular pathways. Many previous studies have explored the impact of these insertions, referred to as NumtS, but have focused primarily on older events that have become fixed and are therefore present in all individual genomes for a given species. We previously developed an approach to identify novel Numt polymorphisms from next-generation sequence data and applied it to thousands of human genomes. Here, we extend this analysis to 79 individuals of other great ape species including chimpanzee, bonobo, gorilla, orang-utan and also an old world monkey, macaque. We show that recent Numt insertions are prevalent in each species though at different apparent rates, with chimpanzees exhibiting a significant increase in both polymorphic and fixed Numt sequences as compared to other great apes. We further assessed positional effects in each species in terms of evolutionary time and rate of insertion and identified putative hotspots on chromosome 5 for Numt integration, providing insight into both recent polymorphic and older fixed reference NumtS in great apes in comparison to human events.Funding: National Institutes of Health (1R01HG007068-01A1 to R.E.M). T.M.B is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 864203), BFU2017-86471-P (MINECO/FEDER, UE), “Unidad de Excelencia María de Maeztu”, funded by the AEI (CEX2018-000792-M), Howard Hughes International Early Career, Obra Social "La Caixa" and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880

Transcriptomic and small RNA response to Mayaro virus infection in Anopheles stephensi mosquitoes

Mayaro virus (MAYV) is an arboviral pathogen in the genus Alphavirus that is circulating in South America with potential to spread to naïve regions. MAYV is also one of the few viruses with the ability to be transmitted by mosquitoes in the genus Anopheles, as well as the typical arboviral transmitting mosquitoes in the genus Aedes. Few studies have investigated the infection response of Anopheles mosquitoes. In this study we detail the transcriptomic and small RNA responses of An. stephensi to infection with MAYV via infectious bloodmeal at 2, 7, and 14 days post infection (dpi). 487 unique transcripts were significantly regulated, 78 putative novel miRNAs were identified, and an siRNA response is observed targeting the MAYV genome. Gene ontology analysis of transcripts regulated at each timepoint shows a number of proteases regulated at 2 and 7 dpi, potentially representative of Toll or melanization pathway activation, and repression of pathways related to autophagy and apoptosis at 14 dpi. These findings provide a basic understanding of the infection response of An. stephensi to MAYV and help to identify host factors which might be useful to target to inhibit viral replication in Anopheles mosquitoes

Challenges and recommendations to improve the installability and archival stability of omics computational tools.

Developing new software tools for analysis of large-scale biological data is a key component of advancing modern biomedical research. Scientific reproduction of published findings requires running computational tools on data generated by such studies, yet little attention is presently allocated to the installability and archival stability of computational software tools. Scientific journals require data and code sharing, but none currently require authors to guarantee the continuing functionality of newly published tools. We have estimated the archival stability of computational biology software tools by performing an empirical analysis of the internet presence for 36,702 omics software resources published from 2005 to 2017. We found that almost 28% of all resources are currently not accessible through uniform resource locators (URLs) published in the paper they first appeared in. Among the 98 software tools selected for our installability test, 51% were deemed "easy to install," and 28% of the tools failed to be installed at all because of problems in the implementation. Moreover, for papers introducing new software, we found that the number of citations significantly increased when authors provided an easy installation process. We propose for incorporation into journal policy several practical solutions for increasing the widespread installability and archival stability of published bioinformatics software