ArticleCell systems2020
BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain.
Erratum issuedOpen access · bronzeAbstract readDataset
In one paragraph
Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
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Corrections and comments
- Erratum issued
Authors and funding
35 authors at 12 institutions in 3 countries.
Reza PourhaghighiDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Peter E A AshDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Sadhna PhanseDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Regina, Regina, SK, Canada; Center for Network Systems Biology, Boston University, Boston, MA, USA.
Florian GoebelsDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Lucas Z M HuDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Siwei ChenDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA.
Yingying ZhangDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA.
Shayne D WierbowskiDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA.
Samantha BoudeauDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Mohamed T MoutaoufikDepartment of Biochemistry, University of Regina, Regina, SK, Canada.
Ramy H MaltyDepartment of Biochemistry, University of Regina, Regina, SK, Canada.
Edyta MalolepszaDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
Kalliopi TsafouDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
Aparna NathanDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
Graham CromarProgram in Molecular Medicine, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Hongbo GuoDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Ali Al AbdullatifDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Daniel J ApiccoDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Lindsay A BeckerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Stefan M PulstDepartment of Neurology, University of Utah, Salt Lake City, UT, USA.
Ahmed YoussefProgram in Bioinformatics, Boston University, Boston, MA, USA; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA.
Ryan HekmanCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA.
Pierre C HavugimanaCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA; Departments of Biochemistry and Biology, Boston University, Boston, MA, USA.
Carl A WhiteCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA.
Benjamin C BlumCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA.
Antonia RattiDepartment of Neurology and Laboratory of Neuroscience, IRCCS, Milan, Italy.
Camron D BryantDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
John ParkinsonProgram in Molecular Medicine, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Kasper LageDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
Mohan BabuDepartment of Biochemistry, University of Regina, Regina, SK, Canada.
Haiyuan YuDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA.
Gary D BaderDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Benjamin WolozinDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Program in Neuroscience, Boston University, Boston, MA, USA. Electronic address: bwolozin@bu.edu.
Andrew EmiliDonnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Program in Bioinformatics, Boston University, Boston, MA, USA; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA; Departments of Biochemistry and Biology, Boston University, Boston, MA, USA. Electronic address: aemili@bu.edu.
Boston University · USUniversity of Toronto · CACornell University · USUniversity of Regina · CACenter for Systems Biology · USMassachusetts General Hospital · USStanford University · USHarvard University · USHospital for Sick Children · CAIstituti di Ricovero e Cura a Carattere Scientifico · ITMassachusetts Institute of Technology · USUniversity of Utah · US
Funding
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MPathway Commons: Research Resource for Biological PathwaysU41HG006623 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI SANDER, CHRIS · 2012 to 2017
$5.7MCytoscape: A Modeling Platform for Biomolecular NetworksR01GM070743 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2004 to 2016
$5.7MCapturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteinsRF1AG056318 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LI, HU, WOLOZIN, BENJAMIN L · 2018 to 2020
$4.4MStress Granules and the Biology of TDP-43R01ES020395 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WOLOZIN, BENJAMIN L · 2012 to 2016
$4.1MSystems-level functional proteomics analysis assemblies in Alzheimer's disease and mouse models of tauopathyRF1AG061706 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI EMILI, ANDREW, WOLOZIN, BENJAMIN L · 2019 to 2019
$3.9MGenetic Modifiers of Protein Interaction Networks in TauopathyR01AG064932 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI EMILI, ANDREW, WOLOZIN, BENJAMIN L · 2019 to 2023
$3.2MRNA binding proteins as novel targets in Alzheimer's diseaseR01AG050471 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WOLOZIN, BENJAMIN L · 2015 to 2019
$2.9MThe role of acetylation in regulating pathophysiology of tauR01NS089544 · NINDS · MAYO CLINIC JACKSONVILLE · PI PETRUCELLI, LEONARD, WOLOZIN, BENJAMIN L · 2014 to 2018
$1.9MSupplement to: PHYSICAL AND FUNCTIONAL SYSTEMS ANALYSIS OF MAMMALIAN MITOCHONDRIAR01GM106019 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BABU, MOHAN, NUNNARI, JODI M. · 2013 to 2016
$954kRegulation of brain neuroprotection and inflammation by TIA1R21AG059925 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WOLOZIN, BENJAMIN L · 2018 to 2019
$454kNHGRI NIH HHS T32 HG002295NHGRI NIH HHS U41 HG006623NIA NIH HHS R01 AG050471NIA NIH HHS R01 AG064932NIA NIH HHS R21 AG059925NIA NIH HHS RF1 AG056318NIA NIH HHS RF1 AG061706NIEHS NIH HHS R01 ES020395NIGMS NIH HHS P41 GM103504NIGMS NIH HHS R01 GM070743NIGMS NIH HHS R01 GM106019NIH HHS S10 OD023663NINDS NIH HHS R01 NS089544
Abstract
Connectivity webs mediate the unique biology of the mammalian brain. Yet, while cell circuit maps are increasingly available, knowledge of their underlying molecular networks remains limited. Here, we applied multi-dimensional biochemical fractionation with mass spectrometry and machine learning to survey endogenous macromolecules across the adult mouse brain. We defined a global "interactome" comprising over one thousand multi-protein complexes. These include hundreds of brain-selective assemblies that have distinct physical and functional attributes, show regional and cell-type specificity, and have links to core neurological processes and disorders. Using reciprocal pull-downs and a transgenic model, we validated a putative 28-member RNA-binding protein complex associated with amyotrophic lateral sclerosis, suggesting a coordinated function in alternative splicing in disease progression. This brain interaction map (BraInMap) resource facilitates mechanistic exploration of the unique molecular machinery driving core cellular processes of the central nervous system. It is publicly available and can be explored here https://www.bu.edu/dbin/cnsb/mousebrain/.
Indexed as
Amyotrophic Lateral SclerosisAnimalsBrainBrain MappingConnectomeDNA-Binding ProteinsMachine LearningMammalsMass SpectrometryMiceMutationDNA-Binding ProteinsALSBraInMapcofractionation/mass spectometrycomplexosomeinteraction networkmachine learningneurodegenerationprotein-protein interactionTDP-43
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Read underepoch 390
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.