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{
"abstracts": [
{
"content": "Discovering all the genetic causes of a phenotype is an important goal in\nfunctional genomics. In this paper we combine an experimental design for\nmultiple independent detections of the genetic causes of a phenotype, with a\nhigh-throughput sequencing analysis that maximizes sensitivity for\ncomprehensively identifying them. Testing this approach on a set of 24 mutant\nstrains generated for a metabolic phenotype with many known genetic causes, we\nshow that this pathway-based phenotype sequencing analysis greatly improves\nsensitivity of detection compared with previous methods, and reveals a wide\nrange of pathways that can cause this phenotype. We demonstrate our approach on\na metabolic re-engineering phenotype, the PEP/OAA metabolic node in E. coli,\nwhich is crucial to a substantial number of metabolic pathways and under\nrenewed interest for biofuel research. Out of 2157 mutations in these strains,\npathway-phenoseq discriminated just five gene groups (12 genes) as\nstatistically significant causes of the phenotype. Experimentally, these five\ngene groups, and the next two high-scoring pathway-phenoseq groups, either have\na clear connection to the PEP metabolite level or offer an alternative path of\nproducing oxaloacetate (OAA), and thus clearly explain the phenotype. These\nhigh-scoring gene groups also show strong evidence of positive selection\npressure, compared with strictly neutral selection in the rest of the genome.",
"lang": "en",
"mimetype": "text/plain",
"sha1": "fd1f89a43ea07ef7825734043c9d9bd56872300e"
}
],
"contribs": [
{
"index": 0,
"raw_name": "Marc Harper",
"role": "author"
},
{
"index": 1,
"raw_name": "Luisa Gronenberg",
"role": "author"
},
{
"index": 2,
"raw_name": "James Liao",
"role": "author"
},
{
"index": 3,
"raw_name": "Christopher Lee",
"role": "author"
}
],
"ext_ids": {
"arxiv": "1303.0455v1"
},
"extra": {
"arxiv": {
"base_id": "1303.0455",
"categories": [
"q-bio.QM",
"q-bio.GN"
]
}
},
"ident": "unwrwze6znf5xouud35i3jlneq",
"language": "en",
"license_slug": "ARXIV-1.0",
"refs": [],
"release_date": "2013-03-03",
"release_stage": "submitted",
"release_type": "article",
"release_year": 2013,
"revision": "d66823db-c3dd-4981-8d79-6ee5b66b358c",
"state": "active",
"title": "Comprehensive Detection of Genes Causing a Phenotype using Phenotype\n Sequencing and Pathway Analysis",
"version": "v1",
"work_id": "a5fegh5iyrfwpc32y33envrime"
}
|
