Pooled‐matrix protein interaction screens using Barcode Fusion Genetics

Abstract High‐throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will requir...

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Main Authors: Nozomu Yachie, Evangelia Petsalaki, Joseph C Mellor, Jochen Weile, Yves Jacob, Marta Verby, Sedide B Ozturk, Siyang Li, Atina G Cote, Roberto Mosca, Jennifer J Knapp, Minjeong Ko, Analyn Yu, Marinella Gebbia, Nidhi Sahni, Song Yi, Tanya Tyagi, Dayag Sheykhkarimli, Jonathan F Roth, Cassandra Wong, Louai Musa, Jamie Snider, Yi‐Chun Liu, Haiyuan Yu, Pascal Braun, Igor Stagljar, Tong Hao, Michael A Calderwood, Laurence Pelletier, Patrick Aloy, David E Hill, Marc Vidal, Frederick P Roth
Format: Article
Language:English
Published: Springer Nature 2016-04-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20156660
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author Nozomu Yachie
Evangelia Petsalaki
Joseph C Mellor
Jochen Weile
Yves Jacob
Marta Verby
Sedide B Ozturk
Siyang Li
Atina G Cote
Roberto Mosca
Jennifer J Knapp
Minjeong Ko
Analyn Yu
Marinella Gebbia
Nidhi Sahni
Song Yi
Tanya Tyagi
Dayag Sheykhkarimli
Jonathan F Roth
Cassandra Wong
Louai Musa
Jamie Snider
Yi‐Chun Liu
Haiyuan Yu
Pascal Braun
Igor Stagljar
Tong Hao
Michael A Calderwood
Laurence Pelletier
Patrick Aloy
David E Hill
Marc Vidal
Frederick P Roth
author_facet Nozomu Yachie
Evangelia Petsalaki
Joseph C Mellor
Jochen Weile
Yves Jacob
Marta Verby
Sedide B Ozturk
Siyang Li
Atina G Cote
Roberto Mosca
Jennifer J Knapp
Minjeong Ko
Analyn Yu
Marinella Gebbia
Nidhi Sahni
Song Yi
Tanya Tyagi
Dayag Sheykhkarimli
Jonathan F Roth
Cassandra Wong
Louai Musa
Jamie Snider
Yi‐Chun Liu
Haiyuan Yu
Pascal Braun
Igor Stagljar
Tong Hao
Michael A Calderwood
Laurence Pelletier
Patrick Aloy
David E Hill
Marc Vidal
Frederick P Roth
author_sort Nozomu Yachie
collection DOAJ
description Abstract High‐throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome‐scale interaction mapping. Here, we report Barcode Fusion Genetics‐Yeast Two‐Hybrid (BFG‐Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG‐Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein‐pair barcodes that can be quantified via next‐generation sequencing. We applied BFG‐Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG‐Y2H increases the efficiency of protein matrix screening, with quality that is on par with state‐of‐the‐art Y2H methods.
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spelling doaj-art-0a18ae4d6e6e47358d45bf840a728d902025-08-20T04:03:12ZengSpringer NatureMolecular Systems Biology1744-42922016-04-0112411710.15252/msb.20156660Pooled‐matrix protein interaction screens using Barcode Fusion GeneticsNozomu Yachie0Evangelia Petsalaki1Joseph C Mellor2Jochen Weile3Yves Jacob4Marta Verby5Sedide B Ozturk6Siyang Li7Atina G Cote8Roberto Mosca9Jennifer J Knapp10Minjeong Ko11Analyn Yu12Marinella Gebbia13Nidhi Sahni14Song Yi15Tanya Tyagi16Dayag Sheykhkarimli17Jonathan F Roth18Cassandra Wong19Louai Musa20Jamie Snider21Yi‐Chun Liu22Haiyuan Yu23Pascal Braun24Igor Stagljar25Tong Hao26Michael A Calderwood27Laurence Pelletier28Patrick Aloy29David E Hill30Marc Vidal31Frederick P Roth32Donnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDépartement de Virologie, Unité de Génétique Moléculaire des Virus à ARN, Institut PasteurDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoJoint IRB‐BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona)Donnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoWeill Institute for Cell and Molecular Biology, Cornell UniversityCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteDonnelly Centre, University of TorontoCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteLunenfeld‐Tanenbaum Research Institute, Mt. Sinai HospitalJoint IRB‐BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona)Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana‐Farber Cancer InstituteDonnelly Centre, University of TorontoAbstract High‐throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome‐scale interaction mapping. Here, we report Barcode Fusion Genetics‐Yeast Two‐Hybrid (BFG‐Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG‐Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein‐pair barcodes that can be quantified via next‐generation sequencing. We applied BFG‐Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG‐Y2H increases the efficiency of protein matrix screening, with quality that is on par with state‐of‐the‐art Y2H methods.https://doi.org/10.15252/msb.20156660DNA barcodeinteractomenext‐generation sequencingprotein interactionyeast two‐hybrid
spellingShingle Nozomu Yachie
Evangelia Petsalaki
Joseph C Mellor
Jochen Weile
Yves Jacob
Marta Verby
Sedide B Ozturk
Siyang Li
Atina G Cote
Roberto Mosca
Jennifer J Knapp
Minjeong Ko
Analyn Yu
Marinella Gebbia
Nidhi Sahni
Song Yi
Tanya Tyagi
Dayag Sheykhkarimli
Jonathan F Roth
Cassandra Wong
Louai Musa
Jamie Snider
Yi‐Chun Liu
Haiyuan Yu
Pascal Braun
Igor Stagljar
Tong Hao
Michael A Calderwood
Laurence Pelletier
Patrick Aloy
David E Hill
Marc Vidal
Frederick P Roth
Pooled‐matrix protein interaction screens using Barcode Fusion Genetics
Molecular Systems Biology
DNA barcode
interactome
next‐generation sequencing
protein interaction
yeast two‐hybrid
title Pooled‐matrix protein interaction screens using Barcode Fusion Genetics
title_full Pooled‐matrix protein interaction screens using Barcode Fusion Genetics
title_fullStr Pooled‐matrix protein interaction screens using Barcode Fusion Genetics
title_full_unstemmed Pooled‐matrix protein interaction screens using Barcode Fusion Genetics
title_short Pooled‐matrix protein interaction screens using Barcode Fusion Genetics
title_sort pooled matrix protein interaction screens using barcode fusion genetics
topic DNA barcode
interactome
next‐generation sequencing
protein interaction
yeast two‐hybrid
url https://doi.org/10.15252/msb.20156660
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