In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein: protein interaction networks

Edson Luiz Folador, Paulo Vinícius Sanches Daltro de Carvalho, Wanderson Marques Silva, Rafaela Salgado Ferreira, Artur Silva, Michael Gromiha, Preetam Ghosh, Debmalya Barh, Vasco Azevedo, Richard Röttger

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Abstract

BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis.

RESULTS: Here, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous.

CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.

Original languageEnglish
Article number103
JournalBMC Systems Biology
Volume10
ISSN1752-0509
DOIs
Publication statusPublished - 4 Nov 2016

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Corynebacterium pseudotuberculosis
Protein Interaction Maps
Protein Interaction Networks
Protein-protein Interaction
Computer Simulation
Proteins
Protein
Interaction
Drug Discovery
Target
Bacteria
Inhibitor
Infection
Diagnostics
Meats
Drugs
Lymphadenitis
Molecules
Wool
Economics

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Folador, Edson Luiz ; de Carvalho, Paulo Vinícius Sanches Daltro ; Silva, Wanderson Marques ; Ferreira, Rafaela Salgado ; Silva, Artur ; Gromiha, Michael ; Ghosh, Preetam ; Barh, Debmalya ; Azevedo, Vasco ; Röttger, Richard. / In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein : protein interaction networks. In: BMC Systems Biology. 2016 ; Vol. 10.
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title = "In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein: protein interaction networks",
abstract = "BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis.RESULTS: Here, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous.CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.",
author = "Folador, {Edson Luiz} and {de Carvalho}, {Paulo Vin{\'i}cius Sanches Daltro} and Silva, {Wanderson Marques} and Ferreira, {Rafaela Salgado} and Artur Silva and Michael Gromiha and Preetam Ghosh and Debmalya Barh and Vasco Azevedo and Richard R{\"o}ttger",
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month = "11",
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doi = "10.1186/s12918-016-0346-4",
language = "English",
volume = "10",
journal = "B M C Systems Biology",
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In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein : protein interaction networks. / Folador, Edson Luiz; de Carvalho, Paulo Vinícius Sanches Daltro; Silva, Wanderson Marques; Ferreira, Rafaela Salgado; Silva, Artur; Gromiha, Michael; Ghosh, Preetam; Barh, Debmalya; Azevedo, Vasco; Röttger, Richard.

In: BMC Systems Biology, Vol. 10, 103, 04.11.2016.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein

T2 - protein interaction networks

AU - Folador, Edson Luiz

AU - de Carvalho, Paulo Vinícius Sanches Daltro

AU - Silva, Wanderson Marques

AU - Ferreira, Rafaela Salgado

AU - Silva, Artur

AU - Gromiha, Michael

AU - Ghosh, Preetam

AU - Barh, Debmalya

AU - Azevedo, Vasco

AU - Röttger, Richard

PY - 2016/11/4

Y1 - 2016/11/4

N2 - BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis.RESULTS: Here, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous.CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.

AB - BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis.RESULTS: Here, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous.CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.

U2 - 10.1186/s12918-016-0346-4

DO - 10.1186/s12918-016-0346-4

M3 - Journal article

VL - 10

JO - B M C Systems Biology

JF - B M C Systems Biology

SN - 1752-0509

M1 - 103

ER -