Cargando…
Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage
BACKGROUND: Development of sensitive sequence search procedures for the detection of distant relationships between proteins at superfamily/fold level is still a big challenge. The intermediate sequence search approach is the most frequently employed manner of identifying remote homologues effectivel...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577913/ https://www.ncbi.nlm.nih.gov/pubmed/23437136 http://dx.doi.org/10.1371/journal.pone.0056449 |
_version_ | 1782260002966208512 |
---|---|
author | Kaushik, Swati Mutt, Eshita Chellappan, Ajithavalli Sankaran, Sandhya Srinivasan, Narayanaswamy Sowdhamini, Ramanathan |
author_facet | Kaushik, Swati Mutt, Eshita Chellappan, Ajithavalli Sankaran, Sandhya Srinivasan, Narayanaswamy Sowdhamini, Ramanathan |
author_sort | Kaushik, Swati |
collection | PubMed |
description | BACKGROUND: Development of sensitive sequence search procedures for the detection of distant relationships between proteins at superfamily/fold level is still a big challenge. The intermediate sequence search approach is the most frequently employed manner of identifying remote homologues effectively. In this study, examination of serine proteases of prolyl oligopeptidase, rhomboid and subtilisin protein families were carried out using plant serine proteases as queries from two genomes including A. thaliana and O. sativa and 13 other families of unrelated folds to identify the distant homologues which could not be obtained using PSI-BLAST. METHODOLOGY/PRINCIPAL FINDINGS: We have proposed to start with multiple queries of classical serine protease members to identify remote homologues in families, using a rigorous approach like Cascade PSI-BLAST. We found that classical sequence based approaches, like PSI-BLAST, showed very low sequence coverage in identifying plant serine proteases. The algorithm was applied on enriched sequence database of homologous domains and we obtained overall average coverage of 88% at family, 77% at superfamily or fold level along with specificity of ∼100% and Mathew’s correlation coefficient of 0.91. Similar approach was also implemented on 13 other protein families representing every structural class in SCOP database. Further investigation with statistical tests, like jackknifing, helped us to better understand the influence of neighbouring protein families. CONCLUSIONS/SIGNIFICANCE: Our study suggests that employment of multiple queries of a family for the Cascade PSI-BLAST searches is useful for predicting distant relationships effectively even at superfamily level. We have proposed a generalized strategy to cover all the distant members of a particular family using multiple query sequences. Our findings reveal that prior selection of sequences as query and the presence of neighbouring families can be important for covering the search space effectively in minimal computational time. This study also provides an understanding of the ‘bridging’ role of related families. |
format | Online Article Text |
id | pubmed-3577913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35779132013-02-22 Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage Kaushik, Swati Mutt, Eshita Chellappan, Ajithavalli Sankaran, Sandhya Srinivasan, Narayanaswamy Sowdhamini, Ramanathan PLoS One Research Article BACKGROUND: Development of sensitive sequence search procedures for the detection of distant relationships between proteins at superfamily/fold level is still a big challenge. The intermediate sequence search approach is the most frequently employed manner of identifying remote homologues effectively. In this study, examination of serine proteases of prolyl oligopeptidase, rhomboid and subtilisin protein families were carried out using plant serine proteases as queries from two genomes including A. thaliana and O. sativa and 13 other families of unrelated folds to identify the distant homologues which could not be obtained using PSI-BLAST. METHODOLOGY/PRINCIPAL FINDINGS: We have proposed to start with multiple queries of classical serine protease members to identify remote homologues in families, using a rigorous approach like Cascade PSI-BLAST. We found that classical sequence based approaches, like PSI-BLAST, showed very low sequence coverage in identifying plant serine proteases. The algorithm was applied on enriched sequence database of homologous domains and we obtained overall average coverage of 88% at family, 77% at superfamily or fold level along with specificity of ∼100% and Mathew’s correlation coefficient of 0.91. Similar approach was also implemented on 13 other protein families representing every structural class in SCOP database. Further investigation with statistical tests, like jackknifing, helped us to better understand the influence of neighbouring protein families. CONCLUSIONS/SIGNIFICANCE: Our study suggests that employment of multiple queries of a family for the Cascade PSI-BLAST searches is useful for predicting distant relationships effectively even at superfamily level. We have proposed a generalized strategy to cover all the distant members of a particular family using multiple query sequences. Our findings reveal that prior selection of sequences as query and the presence of neighbouring families can be important for covering the search space effectively in minimal computational time. This study also provides an understanding of the ‘bridging’ role of related families. Public Library of Science 2013-02-20 /pmc/articles/PMC3577913/ /pubmed/23437136 http://dx.doi.org/10.1371/journal.pone.0056449 Text en © 2013 Kaushik et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kaushik, Swati Mutt, Eshita Chellappan, Ajithavalli Sankaran, Sandhya Srinivasan, Narayanaswamy Sowdhamini, Ramanathan Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage |
title | Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage |
title_full | Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage |
title_fullStr | Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage |
title_full_unstemmed | Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage |
title_short | Improved Detection of Remote Homologues Using Cascade PSI-BLAST: Influence of Neighbouring Protein Families on Sequence Coverage |
title_sort | improved detection of remote homologues using cascade psi-blast: influence of neighbouring protein families on sequence coverage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577913/ https://www.ncbi.nlm.nih.gov/pubmed/23437136 http://dx.doi.org/10.1371/journal.pone.0056449 |
work_keys_str_mv | AT kaushikswati improveddetectionofremotehomologuesusingcascadepsiblastinfluenceofneighbouringproteinfamiliesonsequencecoverage AT mutteshita improveddetectionofremotehomologuesusingcascadepsiblastinfluenceofneighbouringproteinfamiliesonsequencecoverage AT chellappanajithavalli improveddetectionofremotehomologuesusingcascadepsiblastinfluenceofneighbouringproteinfamiliesonsequencecoverage AT sankaransandhya improveddetectionofremotehomologuesusingcascadepsiblastinfluenceofneighbouringproteinfamiliesonsequencecoverage AT srinivasannarayanaswamy improveddetectionofremotehomologuesusingcascadepsiblastinfluenceofneighbouringproteinfamiliesonsequencecoverage AT sowdhaminiramanathan improveddetectionofremotehomologuesusingcascadepsiblastinfluenceofneighbouringproteinfamiliesonsequencecoverage |