Chromosome-wise Protein Interaction Patterns and Their Impact on Functional Implications of Large-Scale Genomic Aberrations
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Chromosome-wise Protein Interaction Patterns and Their Impact on Functional Implications of Large-Scale Genomic Aberrations. / Kirk, Isa Kristina; Weinhold, Nils; Belling, Kirstine; Skakkebæk, Niels Erik; Jensen, Thomas Skøt; Leffers, Henrik; Juul, Anders; Brunak, Søren.
In: Cell Systems, Vol. 4, No. 3, 357-364.e3, 22.03.2017.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Chromosome-wise Protein Interaction Patterns and Their Impact on Functional Implications of Large-Scale Genomic Aberrations
AU - Kirk, Isa Kristina
AU - Weinhold, Nils
AU - Belling, Kirstine
AU - Skakkebæk, Niels Erik
AU - Jensen, Thomas Skøt
AU - Leffers, Henrik
AU - Juul, Anders
AU - Brunak, Søren
N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2017/3/22
Y1 - 2017/3/22
N2 - Gene copy-number changes influence phenotypes through gene-dosage alteration and subsequent changes of protein complex stoichiometry. Human trisomies where gene copy numbers are increased uniformly over entire chromosomes provide generic cases for studying these relationships. In most trisomies, gene and protein level alterations have fatal consequences. We used genome-wide protein-protein interaction data to identify chromosome-specific patterns of protein interactions. We found that some chromosomes encode proteins that interact infrequently with each other, chromosome 21 in particular. We combined the protein interaction data with transcriptome data from human brain tissue to investigate how this pattern of global interactions may affect cellular function. We identified highly connected proteins that also had coordinated gene expression. These proteins were associated with important neurological functions affecting the characteristic phenotypes for Down syndrome and have previously been validated in mouse knockout experiments. Our approach is general and applicable to other gene-dosage changes, such as arm-level amplifications in cancer.
AB - Gene copy-number changes influence phenotypes through gene-dosage alteration and subsequent changes of protein complex stoichiometry. Human trisomies where gene copy numbers are increased uniformly over entire chromosomes provide generic cases for studying these relationships. In most trisomies, gene and protein level alterations have fatal consequences. We used genome-wide protein-protein interaction data to identify chromosome-specific patterns of protein interactions. We found that some chromosomes encode proteins that interact infrequently with each other, chromosome 21 in particular. We combined the protein interaction data with transcriptome data from human brain tissue to investigate how this pattern of global interactions may affect cellular function. We identified highly connected proteins that also had coordinated gene expression. These proteins were associated with important neurological functions affecting the characteristic phenotypes for Down syndrome and have previously been validated in mouse knockout experiments. Our approach is general and applicable to other gene-dosage changes, such as arm-level amplifications in cancer.
U2 - 10.1016/j.cels.2017.01.001
DO - 10.1016/j.cels.2017.01.001
M3 - Journal article
C2 - 28215527
VL - 4
JO - Cell Systems
JF - Cell Systems
SN - 2405-4712
IS - 3
M1 - 357-364.e3
ER -
ID: 174800738