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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2015-02, Vol.10 (2), p.e0118288-e0118288
Main Authors: Ortiz, Maria Teresa Lara, Rosario, Pablo Benjamín Leon, Luna-Nevarez, Pablo, Gamez, Alba Savin, Martínez-del Campo, Ana, Del Rio, Gabriel
Format: Article
Language:English
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0118288