title: Quality control test for sequence-phenotype assignments.
abstract: 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.
authors.affiliation: Department of Biochemistry and Structural Biology. Instituto de Fisiología Celular at the Universidad Nacional Autónoma de México, México DF, 04510, México.
authors.forename: Maria Teresa Lara
authors.initials: MT
authors.lastname: Ortiz
authors.affiliation: Department of Biochemistry and Structural Biology. Instituto de Fisiología Celular at the Universidad Nacional Autónoma de México, México DF, 04510, México.
authors.forename: Pablo Benjamín Leon
authors.initials: PB
authors.lastname: Rosario
authors.affiliation: Department of agronomical sciences and veterinary. Sonora Institute of Technology, Obregon city 85000, Mexico.
authors.forename: Pablo
authors.initials: P
authors.lastname: Luna-Nevarez
authors.affiliation: Department of Biochemistry and Structural Biology. Instituto de Fisiología Celular at the Universidad Nacional Autónoma de México, México DF, 04510, México.
authors.forename: Alba Savin
authors.initials: AS
authors.lastname: Gamez
authors.affiliation: Department of Genetics. Instituto de Fisiología Celular at the Universidad Nacional Autónoma de México, México DF, 04510, México.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-del Campo
authors.affiliation: Department of Biochemistry and Structural Biology. Instituto de Fisiología Celular at the Universidad Nacional Autónoma de México, México DF, 04510, México.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Del Rio
mesh_terms: D004247:DNA / Q000032:analysis*; D059014:High-Throughput Nucleotide Sequencing / Q000592:standards; D020407:Internet; D016296:Mutagenesis; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011786:Quality Control; D017422:Sequence Analysis, DNA / Q000379:methods* / Q000592:standards; D014584:User-Computer Interface
chemical_list: D011506:Proteins; D004247:DNA