A Noise Trimming and Positional Significance of Transposon Insertion System to Identify Essential Genes in Yersinia pestis.
Massively parallel sequencing technology coupled with saturation mutagenesis has provided new and global insights into gene functions and roles. At a simplistic level, the frequency of mutations within genes can indicate the degree of essentiality. However, this approach neglects to take account of the positional significance of mutations - the function of a gene is less likely to be disrupted by a mutation close to the distal ends. Therefore, a systematic bioinformatics approach to improve the reliability of essential gene identification is desirable. We report here a parametric model which introduces a novel mutation feature together with a noise trimming approach to predict the biological significance of Tn5 mutations. We show improved performance of essential gene prediction in the bacterium Yersinia pestis, the causative agent of plague. This method would have broad applicability to other organisms and to the identification of genes which are essential for competitiveness or survival under a broad range of stresses.
Biosciences, University of Exeter, Exeter, EX4 4QD, UK.
Zheng Rong
ZR
Yang
DSTL, Porton Down, Salisbury, SP4 0JQ, UK.
Helen L
HL
Bullifent
Biosciences, University of Exeter, Exeter, EX4 4QD, UK.
Karen
K
Moore
Biosciences, University of Exeter, Exeter, EX4 4QD, UK.
Konrad
K
Paszkiewicz
DSTL, Porton Down, Salisbury, SP4 0JQ, UK.
Richard J
RJ
Saint
DSTL, Porton Down, Salisbury, SP4 0JQ, UK.
Stephanie J
SJ
Southern
Biosciences, University of Exeter, Exeter, EX4 4QD, UK.
Olivia L
OL
Champion
Biosciences, University of Exeter, Exeter, EX4 4QD, UK.
Nicola J
NJ
Senior
DSTL, Porton Down, Salisbury, SP4 0JQ, UK.|Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
Mitali
M
Sarkar-Tyson
DSTL, Porton Down, Salisbury, SP4 0JQ, UK.
Petra C F
PC
Oyston
DSTL, Porton Down, Salisbury, SP4 0JQ, UK.
Timothy P
TP
Atkins
Biosciences, University of Exeter, Exeter, EX4 4QD, UK.
Richard W
RW
Titball
D001426:Bacterial Proteins / Q000235:genetics*; D019295:Computational Biology; D015964:Gene Expression Regulation, Bacterial; D020043:Genes, Essential; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D009154:Mutation; D010641:Phenotype; D010930:Plague / Q000382:microbiology*; D014774:Virulence; D015010:Yersinia pestis / Q000235:genetics* / Q000254:growth & development*
D001426:Bacterial Proteins