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Quality control test for sequence-phenotype assignments
Relating a gene mutation to a phenotype is a common task in different disciplines such as protein biochemistry. In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may intro...
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| Published in: | PloS one 2015-02, Vol.10 (2), p.e0118288-e0118288 |
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| container_end_page | e0118288 |
| container_issue | 2 |
| container_start_page | e0118288 |
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| creator | Ortiz, Maria Teresa Lara Rosario, Pablo Benjamín Leon Luna-Nevarez, Pablo Gamez, Alba Savin Martínez-del Campo, Ana Del Rio, Gabriel |
| description | Relating a gene mutation to a phenotype is a common task in different disciplines such as protein biochemistry. In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may introduce additional false relationships arising from experimental errors. Here we introduce the use of high-throughput DNA sequencers and statistical analysis aimed to identify incorrect DNA sequence-phenotype assignments and observed that 10-20% of these false assignments are expected in large screenings aimed to identify critical residues for protein function. We further show that this level of incorrect DNA sequence-phenotype assignments may significantly alter our understanding about the structure-function relationship of proteins. We have made available an implementation of our method at http://bis.ifc.unam.mx/en/software/chispas. |
| doi_str_mv | 10.1371/journal.pone.0118288 |
| format | article |
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In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may introduce additional false relationships arising from experimental errors. Here we introduce the use of high-throughput DNA sequencers and statistical analysis aimed to identify incorrect DNA sequence-phenotype assignments and observed that 10-20% of these false assignments are expected in large screenings aimed to identify critical residues for protein function. We further show that this level of incorrect DNA sequence-phenotype assignments may significantly alter our understanding about the structure-function relationship of proteins. We have made available an implementation of our method at http://bis.ifc.unam.mx/en/software/chispas.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0118288</identifier><identifier>PMID: 25700273</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biochemistry ; Biology ; Deoxyribonucleic acid ; Dihydrofolate reductase ; DNA ; DNA - analysis ; DNA sequencing ; E coli ; Escherichia coli ; Experiments ; Gene mutation ; Genes ; Genotype & phenotype ; High-Throughput Nucleotide Sequencing - standards ; Internet ; Methods ; Mutagenesis ; Mutation ; Nucleotide sequence ; Phenotype ; Phenotypes ; Point mutation ; Proteins ; Proteins - chemistry ; Proteins - genetics ; Proteins - metabolism ; Quality Control ; Research methodology ; Sequence Analysis, DNA - methods ; Sequence Analysis, DNA - standards ; Statistical analysis ; Structure-function relationships ; User-Computer Interface</subject><ispartof>PloS one, 2015-02, Vol.10 (2), p.e0118288-e0118288</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Ortiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Ortiz et al 2015 Ortiz et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c52d0581d8b912a6cd8267038a692f616605199fe2f503958dd1085ba16a42943</citedby><cites>FETCH-LOGICAL-c692t-c52d0581d8b912a6cd8267038a692f616605199fe2f503958dd1085ba16a42943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1656586405/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1656586405?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25700273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cai, Tao</contributor><creatorcontrib>Ortiz, Maria Teresa Lara</creatorcontrib><creatorcontrib>Rosario, Pablo Benjamín Leon</creatorcontrib><creatorcontrib>Luna-Nevarez, Pablo</creatorcontrib><creatorcontrib>Gamez, Alba Savin</creatorcontrib><creatorcontrib>Martínez-del Campo, Ana</creatorcontrib><creatorcontrib>Del Rio, Gabriel</creatorcontrib><title>Quality control test for sequence-phenotype assignments</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Relating a gene mutation to a phenotype is a common task in different disciplines such as protein biochemistry. In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may introduce additional false relationships arising from experimental errors. Here we introduce the use of high-throughput DNA sequencers and statistical analysis aimed to identify incorrect DNA sequence-phenotype assignments and observed that 10-20% of these false assignments are expected in large screenings aimed to identify critical residues for protein function. We further show that this level of incorrect DNA sequence-phenotype assignments may significantly alter our understanding about the structure-function relationship of proteins. 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| ispartof | PloS one, 2015-02, Vol.10 (2), p.e0118288-e0118288 |
| issn | 1932-6203 1932-6203 |
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| subjects | Biochemistry Biology Deoxyribonucleic acid Dihydrofolate reductase DNA DNA - analysis DNA sequencing E coli Escherichia coli Experiments Gene mutation Genes Genotype & phenotype High-Throughput Nucleotide Sequencing - standards Internet Methods Mutagenesis Mutation Nucleotide sequence Phenotype Phenotypes Point mutation Proteins Proteins - chemistry Proteins - genetics Proteins - metabolism Quality Control Research methodology Sequence Analysis, DNA - methods Sequence Analysis, DNA - standards Statistical analysis Structure-function relationships User-Computer Interface |
| title | Quality control test for sequence-phenotype assignments |
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