Uncovering disease-disease relationships through the incomplete interactome
Open accessAbstract
A network approach to finding disease modules: Shared genes represent a powerful but limited representation of the mechanistic relationship between two diseases. However, the analysis of protein-protein interactions has been hampered by the incompleteness of interactome maps. Menche et al. formulated the mathematical conditions needed to allow a disease module (a localized region of connections between disease-related proteins) to be observed. Only diseases with data coverage that exceeds a specific threshold have identifiable disease modules. The network-based distance between two disease modules revealed that disease pairs that are predicted to have overlapping modules had statistically significant molecular similarity. These similarities encompassed their protein components, gene expression, symptoms, and morbidity. Molecular-level links between diseases lacking shared disease genes could also be identified. Science , this issue 10.1126/science.1257601
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- Authors
- Menche, J., Sharma, A., Kitsak, M., Ghiassian, S. D., Vidal, M., Loscalzo, J., & Barabási, A.-L.
- Affiliations
- Northeastern University (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Center for Complex Networks Research and Department of Physics, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115, USA.
- Venue
- Science
- Published
- 2015-02-20
- Volume
- 347
- Issue
- 6224
- Pages
- 1257601-1257601
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4435741
- OpenAlex
- W2056782561
- Cited by
- 1,546
- References
- 108
- Citations by year
- 2026: 110 · 2025: 112 · 2024: 128 · 2023: 131 · 2022: 142 · 2021: 188 · 2020: 180 · 2019: 149 · 2018: 160 · 2017: 111 · 2016: 98 · 2015: 37
- FWCI
- 58.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P50-HG004233, U01-HG001715)
- NHLBI (PO1-HL083069, R37-HL061795, RC2-HL101543, U01-HL108630)
- NHGRI (UO1-HG007690)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- human interactome, symptom similarity, comorbidities
- MeSH terms
- Disease, Humans, Information Services, Comorbidity, Genetic Predisposition to Disease, Protein Interaction Maps
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