PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.

It has been acknowledged that source databases recording experimentally supported human protein-protein interactions (PPIs) exhibit limited overlap. Thus, the reconstruction of a comprehensive PPI network requires appropriate integration of multiple heterogeneous primary datasets, presenting the PPI...

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Main Authors: Aris Gioutlakis, Maria I Klapa, Nicholas K Moschonas
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5638325?pdf=render
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author Aris Gioutlakis
Maria I Klapa
Nicholas K Moschonas
author_facet Aris Gioutlakis
Maria I Klapa
Nicholas K Moschonas
author_sort Aris Gioutlakis
collection DOAJ
description It has been acknowledged that source databases recording experimentally supported human protein-protein interactions (PPIs) exhibit limited overlap. Thus, the reconstruction of a comprehensive PPI network requires appropriate integration of multiple heterogeneous primary datasets, presenting the PPIs at various genetic reference levels. Existing PPI meta-databases perform integration via normalization; namely, PPIs are merged after converted to a certain target level. Hence, the node set of the integrated network depends each time on the number and type of the combined datasets. Moreover, the irreversible a priori normalization process hinders the identification of normalization artifacts in the integrated network, which originate from the nonlinearity characterizing the genetic information flow. PICKLE (Protein InteraCtion KnowLedgebasE) 2.0 implements a new architecture for this recently introduced human PPI meta-database. Its main novel feature over the existing meta-databases is its approach to primary PPI dataset integration via genetic information ontology. Building upon the PICKLE principles of using the reviewed human complete proteome (RHCP) of UniProtKB/Swiss-Prot as the reference protein interactor set, and filtering out protein interactions with low probability of being direct based on the available evidence, PICKLE 2.0 first assembles the RHCP genetic information ontology network by connecting the corresponding genes, nucleotide sequences (mRNAs) and proteins (UniProt entries) and then integrates PPI datasets by superimposing them on the ontology network without any a priori transformations. Importantly, this process allows the resulting heterogeneous integrated network to be reversibly normalized to any level of genetic reference without loss of the original information, the latter being used for identification of normalization biases, and enables the appraisal of potential false positive interactions through PPI source database cross-checking. The PICKLE web-based interface (www.pickle.gr) allows for the simultaneous query of multiple entities and provides integrated human PPI networks at either the protein (UniProt) or the gene level, at three PPI filtering modes.
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spelling doaj.art-b1f43378469a4b42bdefe29985a0d0f42022-12-21T18:57:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011210e018603910.1371/journal.pone.0186039PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.Aris GioutlakisMaria I KlapaNicholas K MoschonasIt has been acknowledged that source databases recording experimentally supported human protein-protein interactions (PPIs) exhibit limited overlap. Thus, the reconstruction of a comprehensive PPI network requires appropriate integration of multiple heterogeneous primary datasets, presenting the PPIs at various genetic reference levels. Existing PPI meta-databases perform integration via normalization; namely, PPIs are merged after converted to a certain target level. Hence, the node set of the integrated network depends each time on the number and type of the combined datasets. Moreover, the irreversible a priori normalization process hinders the identification of normalization artifacts in the integrated network, which originate from the nonlinearity characterizing the genetic information flow. PICKLE (Protein InteraCtion KnowLedgebasE) 2.0 implements a new architecture for this recently introduced human PPI meta-database. Its main novel feature over the existing meta-databases is its approach to primary PPI dataset integration via genetic information ontology. Building upon the PICKLE principles of using the reviewed human complete proteome (RHCP) of UniProtKB/Swiss-Prot as the reference protein interactor set, and filtering out protein interactions with low probability of being direct based on the available evidence, PICKLE 2.0 first assembles the RHCP genetic information ontology network by connecting the corresponding genes, nucleotide sequences (mRNAs) and proteins (UniProt entries) and then integrates PPI datasets by superimposing them on the ontology network without any a priori transformations. Importantly, this process allows the resulting heterogeneous integrated network to be reversibly normalized to any level of genetic reference without loss of the original information, the latter being used for identification of normalization biases, and enables the appraisal of potential false positive interactions through PPI source database cross-checking. The PICKLE web-based interface (www.pickle.gr) allows for the simultaneous query of multiple entities and provides integrated human PPI networks at either the protein (UniProt) or the gene level, at three PPI filtering modes.http://europepmc.org/articles/PMC5638325?pdf=render
spellingShingle Aris Gioutlakis
Maria I Klapa
Nicholas K Moschonas
PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.
PLoS ONE
title PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.
title_full PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.
title_fullStr PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.
title_full_unstemmed PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.
title_short PICKLE 2.0: A human protein-protein interaction meta-database employing data integration via genetic information ontology.
title_sort pickle 2 0 a human protein protein interaction meta database employing data integration via genetic information ontology
url http://europepmc.org/articles/PMC5638325?pdf=render
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AT nicholaskmoschonas pickle20ahumanproteinproteininteractionmetadatabaseemployingdataintegrationviageneticinformationontology