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| A human phenome-interactome network of protein complexes implicated in genetic disorders |
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| Author(s): Lage K (Lage, Kasper), Karlberg EO (Karlberg, E. Olof), Storling ZM (Storling, Zenia M.), Olason PI (Olason, Pall I.), Pedersen AG (Pedersen, Anders G.), Rigina O (Rigina, Olga), Hinsby AM (Hinsby, Anders M.), Tumer Z (Tumer, Zeynep), Pociot F (Pociot, Flemming), Tommerup N (Tommerup, Niels), Moreau Y (Moreau, Yves), Brunak S (Brunak, Soren) |
| Source: NATURE BIOTECHNOLOGY Volume: 25 Issue: 3 Pages: 309-316 Published: MAR 2007 |
| Times Cited: 109 References: 56 |
| Abstract: We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality-controlled interactions of human proteins with a validated, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease. Our publicly available draft of protein complexes associated with pathology comprises 506 complexes, which reveal functional relationships between disease-promoting genes that will inform future experimentation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Brunak, S (reprint author), Tech Univ Denmark, Ctr Biol Sequence Anal, BioCtr STU, Bldg 208, DK-2800 Lyngby, Denmark |
Addresses:
1. Tech Univ Denmark, Ctr Biol Sequence Anal, BioCtr STU, DK-2800 Lyngby, Denmark
2. Univ Copenhagen, Panum Inst, Dept Cellular & Mol Med, Wilhelm Johannsen Ctr Funct Genome Res, DK-2200 Copenhagen N, Denmark
3. Lund Univ, Inst Clin Sci, SE-22100 Lund, Sweden
4. Steno Diabet Ctr, DK-2820 Gentofte, Denmark
5. Katholieke Univ Leuven, Fac Engn, Dept Elect Engn, B-3001 Heverlee, Belgium |
| Publisher: NATURE PUBLISHING GROUP, 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA |
| Subject Category: Biotechnology & Applied Microbiology |
| IDS Number: 143TP |
| ISSN: 1087-0156 |
| DOI: 10.1038/nbt1295 |
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