A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments

Phage Display is a powerful method for the identification of peptide binding to targets of variable complexities and tissues, from unique molecules to the internal surfaces of vessels of living organisms. Particularly for in vivo screenings, the resulting repertoires can be very complex and difficul...

Full description

Bibliographic Details
Main Authors: Antonios Vekris, Eleftherios Pilalis, Aristotelis Chatziioannou, Klaus G. Petry
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2019.01160/full
_version_ 1818941001828401152
author Antonios Vekris
Eleftherios Pilalis
Eleftherios Pilalis
Aristotelis Chatziioannou
Aristotelis Chatziioannou
Klaus G. Petry
author_facet Antonios Vekris
Eleftherios Pilalis
Eleftherios Pilalis
Aristotelis Chatziioannou
Aristotelis Chatziioannou
Klaus G. Petry
author_sort Antonios Vekris
collection DOAJ
description Phage Display is a powerful method for the identification of peptide binding to targets of variable complexities and tissues, from unique molecules to the internal surfaces of vessels of living organisms. Particularly for in vivo screenings, the resulting repertoires can be very complex and difficult to study with traditional approaches. Next Generation Sequencing (NGS) opened the possibility to acquire high resolution overviews of such repertoires and thus facilitates the identification of binders of interest. Additionally, the ever-increasing amount of available genome/proteome information became satisfactory regarding the identification of putative mimicked proteins, due to the large scale on which partial sequence homology is assessed. However, the subsequent production of massive data stresses the need for high-performance computational approaches in order to perform standardized and insightful molecular network analysis. Systems-level analysis is essential for efficient resolution of the underlying molecular complexity and the extraction of actionable interpretation, in terms of systemic biological processes and pathways that are systematically perturbed. In this work we introduce PepSimili, an integrated workflow tool, which performs mapping of massive peptide repertoires on whole proteomes and delivers a streamlined, systems-level biological interpretation. The tool employs modules for modeling and filtering of background noise due to random mappings and amplifies the biologically meaningful signal through coupling with BioInfoMiner, a systems interpretation tool that employs graph-theoretic methods for prioritization of systemic processes and corresponding driver genes. The current implementation exploits the Galaxy environment and is available online. A case study using public data is presented, with and without a control selection.
first_indexed 2024-12-20T06:48:36Z
format Article
id doaj.art-a73ebf520ed149b78d5b4d5d8ab58be3
institution Directory Open Access Journal
issn 1664-042X
language English
last_indexed 2024-12-20T06:48:36Z
publishDate 2019-09-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Physiology
spelling doaj.art-a73ebf520ed149b78d5b4d5d8ab58be32022-12-21T19:49:37ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-09-011010.3389/fphys.2019.01160434562A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display ExperimentsAntonios Vekris0Eleftherios Pilalis1Eleftherios Pilalis2Aristotelis Chatziioannou3Aristotelis Chatziioannou4Klaus G. Petry5UMR 1049 and U1029, INSERM, Bordeaux, FranceMetabolic Engineering and Bioinformatics Program, Institute of Chemical Biology, National Hellenic Research Foundation, Athens, GreeceeNIOS Applications P.C., Athens, GreeceMetabolic Engineering and Bioinformatics Program, Institute of Chemical Biology, National Hellenic Research Foundation, Athens, GreeceeNIOS Applications P.C., Athens, GreeceUMR 1049 and U1029, INSERM, Bordeaux, FrancePhage Display is a powerful method for the identification of peptide binding to targets of variable complexities and tissues, from unique molecules to the internal surfaces of vessels of living organisms. Particularly for in vivo screenings, the resulting repertoires can be very complex and difficult to study with traditional approaches. Next Generation Sequencing (NGS) opened the possibility to acquire high resolution overviews of such repertoires and thus facilitates the identification of binders of interest. Additionally, the ever-increasing amount of available genome/proteome information became satisfactory regarding the identification of putative mimicked proteins, due to the large scale on which partial sequence homology is assessed. However, the subsequent production of massive data stresses the need for high-performance computational approaches in order to perform standardized and insightful molecular network analysis. Systems-level analysis is essential for efficient resolution of the underlying molecular complexity and the extraction of actionable interpretation, in terms of systemic biological processes and pathways that are systematically perturbed. In this work we introduce PepSimili, an integrated workflow tool, which performs mapping of massive peptide repertoires on whole proteomes and delivers a streamlined, systems-level biological interpretation. The tool employs modules for modeling and filtering of background noise due to random mappings and amplifies the biologically meaningful signal through coupling with BioInfoMiner, a systems interpretation tool that employs graph-theoretic methods for prioritization of systemic processes and corresponding driver genes. The current implementation exploits the Galaxy environment and is available online. A case study using public data is presented, with and without a control selection.https://www.frontiersin.org/article/10.3389/fphys.2019.01160/fullphage displayGalaxy platformenrichment analysisnetwork analysisbiological interpretationReactome
spellingShingle Antonios Vekris
Eleftherios Pilalis
Eleftherios Pilalis
Aristotelis Chatziioannou
Aristotelis Chatziioannou
Klaus G. Petry
A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments
Frontiers in Physiology
phage display
Galaxy platform
enrichment analysis
network analysis
biological interpretation
Reactome
title A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments
title_full A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments
title_fullStr A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments
title_full_unstemmed A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments
title_short A Computational Pipeline for the Extraction of Actionable Biological Information From NGS-Phage Display Experiments
title_sort computational pipeline for the extraction of actionable biological information from ngs phage display experiments
topic phage display
Galaxy platform
enrichment analysis
network analysis
biological interpretation
Reactome
url https://www.frontiersin.org/article/10.3389/fphys.2019.01160/full
work_keys_str_mv AT antoniosvekris acomputationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT eleftheriospilalis acomputationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT eleftheriospilalis acomputationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT aristotelischatziioannou acomputationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT aristotelischatziioannou acomputationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT klausgpetry acomputationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT antoniosvekris computationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT eleftheriospilalis computationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT eleftheriospilalis computationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT aristotelischatziioannou computationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT aristotelischatziioannou computationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments
AT klausgpetry computationalpipelinefortheextractionofactionablebiologicalinformationfromngsphagedisplayexperiments