Journal article
Chromosome-wise Protein Interaction Patterns and Their Impact on Functional Implications of Large-Scale Genomic Aberrations
Department of Systems Biology, Technical University of Denmark1
Integrative Systems Biology, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3
University of Copenhagen4
Center for Biological sequence analysis, Technical University of Denmark5
Department of Bio and Health Informatics, Technical University of Denmark6
Integrative Systems Biology, Department of Bio and Health Informatics, Technical University of Denmark7
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.
Language: | English |
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Year: | 2017 |
Pages: | 357-364 |
ISSN: | 24054712 and 24054720 |
Types: | Journal article |
DOI: | 10.1016/j.cels.2017.01.001 |
ORCIDs: | 0000-0001-5664-1948 , 0000-0002-0534-4350 and 0000-0003-0316-5866 |
Animals Chromosome Aberrations Chromosomes Chromosomes, Human, Pair 21 Down Syndrome Gene Dosage Gene Expression Profiling Genomics Humans Mice Oligonucleotide Array Sequence Analysis Protein Interaction Mapping Transcriptome Trisomy aneuploidy genome structure protein complex protein interaction data stoichiometry systems biology topology-associated domain (TAD) trisomy