Dataset Information

A Mouse-Specific Model to Detect Genes under Selection in Tumors.

ABSTRACT: The mouse is a widely used model organism in cancer research. However, no computational methods exist to identify cancer driver genes in mice due to a lack of labeled training data. To address this knowledge gap, we adapted the GUST (Genes Under Selection in Tumors) model, originally trained on human exomes, to mouse exomes via transfer learning. The resulting tool, called GUST-mouse, can estimate long-term and short-term evolutionary selection in mouse tumors, and distinguish between oncogenes, tumor suppressor genes, and passenger genes using high-throughput sequencing data. We applied GUST-mouse to analyze 65 exomes of mouse primary breast cancer models and 17 exomes of mouse leukemia models. Comparing the predictions between cancer types and between human and mouse tumors revealed common and unique driver genes. The GUST-mouse method is available as an open-source R package on github.

SUBMITTER: Chen H

PROVIDER: S-EPMC10647215 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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A Mouse-Specific Model to Detect Genes under Selection in Tumors.

Chen Hai H Shu Jingmin J Maley Carlo C CC Liu Li L

Cancers 20231026 21

The mouse is a widely used model organism in cancer research. However, no computational methods exist to identify cancer driver genes in mice due to a lack of labeled training data. To address this knowledge gap, we adapted the GUST (Genes Under Selection in Tumors) model, originally trained on human exomes, to mouse exomes via transfer learning. The resulting tool, called GUST-mouse, can estimate long-term and short-term evolutionary selection in mouse tumors, and distinguish between oncogenes, ...[more]

PMID: 37958330

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Project description:BACKGROUND:The transition to a parasitic lifestyle entails comprehensive changes to the selective regime. In parasites, genes encoding for traits that facilitate host detection, exploitation and transmission should be under selection. Slavemaking ants are social parasites that exploit the altruistic behaviour of their hosts by stealing heterospecific host brood during raids, which afterwards serve as slaves in slavemaker nests. Here we search for evidence of selection in the transcriptomes of three slavemaker species and three closely related hosts. We expected selection on genes underlying recognition and raiding or defense behaviour. Analyses of selective forces in species with a slavemaker or host lifestyle allowed investigation into whether or not repeated instances of slavemaker evolution share the same genetic basis. To investigate the genetic basis of host-slavemaker co-evolution, we created orthologous clusters from transcriptome sequences of six Temnothorax ant species - three slavemakers and three hosts - to identify genes with signatures of selection. We further tested for functional enrichment in selected genes from slavemakers and hosts respectively and investigated which pathways the according genes belong to. RESULTS:Our phylogenetic analysis, based on more than 5000 ortholog sequences, revealed sister species status for two slavemakers as well as two hosts, contradicting a previous phylogeny based on mtDNA. We identified 309 genes with signs of positive selection on branches leading to slavemakers and 161 leading to hosts. Among these were genes potentially involved in cuticular hydrocarbon synthesis, thus species recognition, and circadian clock functionality possibly explaining the different activity patterns of slavemakers and hosts. There was little overlap of genes with signatures of positive selection among species, which are involved in numerous different functions and different pathways. CONCLUSIONS:We identified different genes, functions and pathways under positive selection in each species. These results point to species-specific adaptations rather than convergent trajectories during the evolution of the slavemaker and host lifestyles suggesting that the evolution of parasitism, even in closely related species, may be achieved in diverse ways.

Dataset Information

A Mouse-Specific Model to Detect Genes under Selection in Tumors.

Publications

A Mouse-Specific Model to Detect Genes under Selection in Tumors.

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