Gene fusion analysis in the battle against the African endemic sleeping sickness.

The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs),...

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Main Authors: Philip Trimpalis, Vassiliki Lila Koumandou, Evangelia Pliakou, Nicholas P Anagnou, Sophia Kossida
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3714255?pdf=render
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author Philip Trimpalis
Vassiliki Lila Koumandou
Evangelia Pliakou
Nicholas P Anagnou
Sophia Kossida
author_facet Philip Trimpalis
Vassiliki Lila Koumandou
Evangelia Pliakou
Nicholas P Anagnou
Sophia Kossida
author_sort Philip Trimpalis
collection DOAJ
description The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs), vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method) was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a) statistical significance (BLAST e-value, domain length etc.), (b) their involvement in crucial metabolic pathways, and (c) their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns.
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spelling doaj.art-0d02930efacb4364bd91a20ff27dab8d2022-12-21T22:37:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6885410.1371/journal.pone.0068854Gene fusion analysis in the battle against the African endemic sleeping sickness.Philip TrimpalisVassiliki Lila KoumandouEvangelia PliakouNicholas P AnagnouSophia KossidaThe protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs), vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method) was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a) statistical significance (BLAST e-value, domain length etc.), (b) their involvement in crucial metabolic pathways, and (c) their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns.http://europepmc.org/articles/PMC3714255?pdf=render
spellingShingle Philip Trimpalis
Vassiliki Lila Koumandou
Evangelia Pliakou
Nicholas P Anagnou
Sophia Kossida
Gene fusion analysis in the battle against the African endemic sleeping sickness.
PLoS ONE
title Gene fusion analysis in the battle against the African endemic sleeping sickness.
title_full Gene fusion analysis in the battle against the African endemic sleeping sickness.
title_fullStr Gene fusion analysis in the battle against the African endemic sleeping sickness.
title_full_unstemmed Gene fusion analysis in the battle against the African endemic sleeping sickness.
title_short Gene fusion analysis in the battle against the African endemic sleeping sickness.
title_sort gene fusion analysis in the battle against the african endemic sleeping sickness
url http://europepmc.org/articles/PMC3714255?pdf=render
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