GeneNetwork: a continuously updated tool for systems genetics analyses

Ashbrook, David G.

doi:10.1101/2020.12.23.424047

Cited by 8 publications

(12 citation statements)

References 44 publications

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“…The data sources employed are available on GEO and gene network 2 (gn2.genenetwork.org) and linked in Supplementary Tables 1, 2. All the collected data involves experiments within the BXD family and mm10 in the search tool (Mulligan et al, 2017;Watson and Ashbrook, 2020). Three datasets included male mice experiments, one both sexes, and three came from experiments on female mice.…”

Section: Data Collectionmentioning

confidence: 99%

Lifespan-Associated Gene Expression Signatures of Recombinant BXD Mice Implicates Coro7 and Set in Longevity

et al. 2021

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Although genetic approaches have identified key genes and pathways that promote longevity, systems-level approaches are less utilized. Here, we took advantage of the wealth of omics data characterizing the BXD family of mice. We associated transcript and peptide levels across five tissues from both female and male BXD isogenic lines with their median lifespan. We identified over 5000 genes that showed a longevity correlation in a given tissue. Surprisingly, we found less than 1% overlap among longevity-correlating genes across tissues and sex. These 1% shared genes consist of 51 genes, of which 13 have been shown to alter lifespan. Only two genes -Coro7 and Set- showed a longevity correlation in all tissues and in both sexes. While differential regulation of aging across tissues and sex has been reported, our systems-level analysis reveals two unique genes that may promote healthy aging in unique sex- and tissue-agnostic manner.

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Section: Data Collectionmentioning

confidence: 99%

Lifespan-Associated Gene Expression Signatures of Recombinant BXD Mice Implicates Coro7 and Set in Longevity

et al. 2021

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“…By extension, phenotypes collected in 2022 will still be informative in 2072. This is made possible not only by the use of well-characterized inbred strains, but by the dedicated community who have donated their data to open access resources, particularly GeneNetwork 22,23,[95][96][97] . In this way, phenotypes collected across decades, continents and environments can be coherently coanalyzed, providing new insight from legacy data 95 .…”

Section: Discussionmentioning

confidence: 99%

Private and sub-family specific mutations of founder haplotypes in the BXD family reveal phenotypic consequences relevant to health and disease

Ashbrook

Sasani

Maksimov

et al. 2022

Preprint

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The BXD recombinant inbred (RI) mouse strains are the largest and most deeply phenotyped inbred panel of vertebrate organisms. RIs allow phenotyping of isogenic individuals across virtually any environment or treatment. We performed whole genome sequencing and generated a compendium of SNPs, indels, short tandem repeats, and structural variants in these strains and used them to analyze phenomic data accumulated over the past 50 years.We show that BXDs segregate >6 million variants with high minor allele which are dervied from the C57BL/6J and DBA/2J founders and use this dense variant set to define ‘infinite’ marker maps and a novel family-level pangenome. We additionally characterize rates and spectra de novo variants which have accumulated over 20-200 generations of inbreeding, and have largely been ignored previously. Overall, the uniquely rich phenome when linked with WGS enables a new type of integrative modeling of genotype-to-phenotype relations.

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“…Shared QTLs, where both the gene-expression and a phenotype of interest are associated with the same locus, provide strong evidence of a genetic link. Using GeneNetwork.org we can build biological networks, moving from genetic variant, to expression difference, to protein expression, to whole-system outcomes, with just a few keystrokes, and without touching a lab bench [134][135][136]. Entire manuscripts can be written without leaving a web browser [137].…”

Section: The Deepest Phenome For Any Familymentioning

confidence: 99%

Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology

Ashbrook¹,

Lu²

2022

Preclinical Animal Modeling in Medicine

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Recombinant inbred rodents form immortal genome-types that can be resampled deeply at many stages, in both sexes, and under multiple experimental conditions to model genome-environment interactions and to test genome-phenome predictions. This allows for experimental precision medicine, for which sophisticated causal models of complex interactions among DNA variants, phenotype variants at many levels, and innumerable environmental factors are required. Large families and populations of isogenic lines of mice and rats are now available and have been used across fields of biology. We will use the BXD recombinant inbred family and their derived diallel cross population as an example for predictive, experimental precision medicine and biology.

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GeneNetwork: a continuously updated tool for systems genetics analyses

Cited by 8 publications

References 44 publications

Lifespan-Associated Gene Expression Signatures of Recombinant BXD Mice Implicates Coro7 and Set in Longevity

Lifespan-Associated Gene Expression Signatures of Recombinant BXD Mice Implicates Coro7 and Set in Longevity

Private and sub-family specific mutations of founder haplotypes in the BXD family reveal phenotypic consequences relevant to health and disease

Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology

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