ArchiHeart - Dataset : Software containers, SQlite database and DGRP data

<strong>Title : </strong>Genetic architecture of natural variation of cardiac performance in flies <strong>Abstract : </strong>Deciphering the genetic architecture of human cardiac disorders is of fundamental importance but their underlying complexity is a major hurdle. We investigated the natural variation of cardiac performance in the sequenced inbred lines of the Drosophila Genetic Reference Panel (DGRP)1. Genome Wide Associations Studies (GWAS) identified genetic networks associated with natural variation of cardiac traits which were extensively validated with <em>in vivo</em> cardiac-specific gene manipulation<em>.</em> Specifically, non-coding variants that we identified were used to map potential regulatory non-coding regions, which in turn were employed to predict Transcription Factors (TFs) binding sites. Cognate TFs, many of which themselves bear polymorphisms associated with variations of cardiac performance, were also validated by heart specific knockdown. Although rarely studied, the genetic control of phenotypic variability is of primary importance, with both medical and fundamental implications. We showed that the natural variations associated with variability in cardiac performance affect a set of genes overlapping with those associated with average traits but through different variants in the same genes. Furthermore, we showed that phenotypic variability is also associated with gene regulatory network deviations. More importantly, we documented correlations between genes associated with cardiac phenotypes in both flies and humans, which supports a conserved genetic architecture regulating adult cardiac function from arthropods to mammals. Specifically, roles for PAX9 and EGR2 in the regulation of the cardiac rhythm were established in both models, illustrating that the characteristics of natural variations in cardiac function identified in Drosophila can accelerate discovery in humans. <strong>Data</strong> : phenosnip_singleageanalysis.img : singularity v2.6 image with R 3.4.4 and python 2.7, used for preliminary statistical analysis. phenosnip_singleagegwas.img : singualrity v2.6 image with FastLMM and plink, used for GWAS analysis phenosnip_singleageepistasis.img : singualrity c2.6 image with fastEpistasis and plink, used for epistasis analysis Phenosnip.sqlite.tar.gz : SQlite database containing the genotype information from DGRP consortium and the phenotype data of the study (1 week aged drosophila) dgrp2.tar.gz : BED, BIM and FAM files with genetic information of the DGRP lines (data issued from the DGRP consortium) datasets_saha_et_al.zip : raw data (individual phenotypes of DGRP lines / variants identified by GWAS / individual phenotypes from validation experiments) and large scale datasets used for analyses (PPI and genetic interactions / regulatory variants)标题：果蝇心脏功能自然变异的遗传架构 摘要：解析人类心脏疾病的遗传架构具有基础性重要意义，但其内在的复杂性是一大主要障碍。本研究针对果蝇遗传参考品系库（Drosophila Genetic Reference Panel, DGRP）1的测序近交系的心脏功能自然变异展开了探究。全基因组关联研究（Genome Wide Associations Studies, GWAS）鉴定出了与心脏性状自然变异相关的遗传网络，并通过体内（in vivo）心脏特异性基因操作进行了广泛验证。具体而言，本研究鉴定出的非编码变异被用于定位潜在的调控非编码区域，进而用于预测转录因子（Transcription Factors, TFs）结合位点。诸多同源转录因子自身携带与心脏功能变异相关的多态性，我们也通过心脏特异性敲低实验对其进行了验证。尽管表型变异的遗传调控鲜有研究，但其兼具医学与基础研究价值，具有首要的重要性。本研究发现，与心脏功能变异相关的自然变异影响了一组与平均性状相关基因存在重叠的基因，但通过同一基因内的不同变异实现调控。此外，本研究证实表型变异还与基因调控网络的偏差存在关联。更为重要的是，我们记录了果蝇与人类心脏表型相关基因之间的关联，这支持了从节肢动物到哺乳动物的成年心脏功能的保守遗传调控架构。具体而言，本研究在两种模型中确立了PAX9与EGR2在心脏节律调控中的作用，表明在果蝇中鉴定出的心脏功能自然变异特征能够加速人类相关研究的发现。 数据： phenosnip_singleageanalysis.img：搭载R 3.4.4与Python 2.7的Singularity v2.6镜像，用于开展初步统计分析。 phenosnip_singleagegwas.img：搭载FastLMM与plink的Singularity v2.6镜像，用于全基因组关联分析。 phenosnip_singleageepistasis.img：搭载fastEpistasis与plink的Singularity v2.6镜像，用于上位性分析。 Phenosnip.sqlite.tar.gz：包含果蝇遗传参考品系库（DGRP）联盟的基因型信息与本研究表型数据（1周龄果蝇）的SQLite数据库。 dgrp2.tar.gz：包含果蝇遗传参考品系库（DGRP）品系遗传信息的BED、BIM与FAM文件（数据来源于DGRP联盟）。 datasets_saha_et_al.zip：包含原始数据（果蝇遗传参考品系库（DGRP）品系的个体表型、全基因组关联研究鉴定的变异、验证实验的个体表型）以及用于分析的大规模数据集（蛋白质相互作用与遗传互作数据、调控变异数据）的压缩包。