Reconstruction of a Genetic Pathway Using Transcriptome Mapping in a Metazoan

Abstract

RNA‐seq is a technique that is commonly used to identify downstream elements to a genetic or chemical perturbation. In theory, global transcriptomes contain enough information to perform a full‐fledged genetic analysis of a pathway. Early attempts to do this using microarrays in single celled organisms reported partial reconstruction of a genetic pathway. Using the hypoxia pathway, we show that genetic reconstructions can be performed using global transcriptome data. We obtained the transcriptomes of 5 C. elegans single mutants and 2 double mutants at the young adult stage. We show that in a blinded computational study, we were able to identify relevant genetic relationships between all genes in a pathway. In addition, we identified a core set of ~500 genes that make up the bulk of the C. elegans hypoxia response. Multiple of these genes are directly implicated in the Electron Transport Chain (ETC), metabolism regulation or chemical damage responses.

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