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PON-P2: Prediction Method for Fast and Reliable Identification of Harmful Variants.

Niroula, Abhishek LU ; Urolagin, Siddhaling LU and Vihinen, Mauno LU (2015) In PLoS ONE 10(2).
Abstract
More reliable and faster prediction methods are needed to interpret enormous amounts of data generated by sequencing and genome projects. We have developed a new computational tool, PON-P2, for classification of amino acid substitutions in human proteins. The method is a machine learning-based classifier and groups the variants into pathogenic, neutral and unknown classes, on the basis of random forest probability score. PON-P2 is trained using pathogenic and neutral variants obtained from VariBench, a database for benchmark variation datasets. PON-P2 utilizes information about evolutionary conservation of sequences, physical and biochemical properties of amino acids, GO annotations and if available, functional annotations of variation... (More)
More reliable and faster prediction methods are needed to interpret enormous amounts of data generated by sequencing and genome projects. We have developed a new computational tool, PON-P2, for classification of amino acid substitutions in human proteins. The method is a machine learning-based classifier and groups the variants into pathogenic, neutral and unknown classes, on the basis of random forest probability score. PON-P2 is trained using pathogenic and neutral variants obtained from VariBench, a database for benchmark variation datasets. PON-P2 utilizes information about evolutionary conservation of sequences, physical and biochemical properties of amino acids, GO annotations and if available, functional annotations of variation sites. Extensive feature selection was performed to identify 8 informative features among altogether 622 features. PON-P2 consistently showed superior performance in comparison to existing state-of-the-art tools. In 10-fold cross-validation test, its accuracy and MCC are 0.90 and 0.80, respectively, and in the independent test, they are 0.86 and 0.71, respectively. The coverage of PON-P2 is 61.7% in the 10-fold cross-validation and 62.1% in the test dataset. PON-P2 is a powerful tool for screening harmful variants and for ranking and prioritizing experimental characterization. It is very fast making it capable of analyzing large variant datasets. PON-P2 is freely available at http://structure.bmc.lu.se/PON-P2/. (Less)
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author
organization
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Contribution to journal
publication status
published
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in
PLoS ONE
volume
10
issue
2
publisher
Public Library of Science
external identifiers
  • pmid:25647319
  • wos:000348822600067
  • scopus:84922351308
ISSN
1932-6203
DOI
10.1371/journal.pone.0117380
language
English
LU publication?
yes
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052fea31-a84d-4087-96b2-ba1299aac0f8 (old id 5145550)
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http://www.ncbi.nlm.nih.gov/pubmed/25647319?dopt=Abstract
date added to LUP
2015-03-03 20:24:04
date last changed
2017-11-19 04:00:15
@article{052fea31-a84d-4087-96b2-ba1299aac0f8,
  abstract     = {More reliable and faster prediction methods are needed to interpret enormous amounts of data generated by sequencing and genome projects. We have developed a new computational tool, PON-P2, for classification of amino acid substitutions in human proteins. The method is a machine learning-based classifier and groups the variants into pathogenic, neutral and unknown classes, on the basis of random forest probability score. PON-P2 is trained using pathogenic and neutral variants obtained from VariBench, a database for benchmark variation datasets. PON-P2 utilizes information about evolutionary conservation of sequences, physical and biochemical properties of amino acids, GO annotations and if available, functional annotations of variation sites. Extensive feature selection was performed to identify 8 informative features among altogether 622 features. PON-P2 consistently showed superior performance in comparison to existing state-of-the-art tools. In 10-fold cross-validation test, its accuracy and MCC are 0.90 and 0.80, respectively, and in the independent test, they are 0.86 and 0.71, respectively. The coverage of PON-P2 is 61.7% in the 10-fold cross-validation and 62.1% in the test dataset. PON-P2 is a powerful tool for screening harmful variants and for ranking and prioritizing experimental characterization. It is very fast making it capable of analyzing large variant datasets. PON-P2 is freely available at http://structure.bmc.lu.se/PON-P2/.},
  articleno    = {e0117380},
  author       = {Niroula, Abhishek and Urolagin, Siddhaling and Vihinen, Mauno},
  issn         = {1932-6203},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {PON-P2: Prediction Method for Fast and Reliable Identification of Harmful Variants.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0117380},
  volume       = {10},
  year         = {2015},
}