Network-Based Biomarkers Enable Cross-Disease Biomarker Discovery
| Autor: | Caroline M. Seynaeve, Pietro Liò, Daniel Rea, Syed Haider, Luc Dirix, Dirk G. Kieback, Cindy Q. Yao, Cheryl Crozier, Christos Markopoulos, Nathalie C. Moon, Francis Nguyen, Annette Hasenburg, Michal R. Grzadkowski, Paul C. Boutros, Camilla Drake, Cassandra Brookes, Maud H.W. Starmans, Philippe Lambin, Stimper, John M. S. Bartlett, van de Velde Cj, Xihui Lin, Arek Kasprzyk, Jean C.Y. Wang, Vicky S Sabine |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Genomic profiling Molecular model Computer science Biodiversity Computational biology Precision medicine 3. Good health 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Disease biomarker Biomarker (medicine) Validation cohort Biological network 030304 developmental biology |
| Popis: | Biomarkers lie at the heart of precision medicine, biodiversity monitoring, agricultural pathogen detection, amongst others. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers almost always involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. We therefore created SIMMS: an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We applied SIMMS to multiple data-types across four diseases, and in each it reproducibly identified subtypes, made superior predictions to the best bespoke approaches, and identified known and novel signaling nodes. To demonstrate its ability on a new dataset, we measured 33 genes/nodes of the PIK3CA pathway in 1,734 FFPE breast tumours and created a four-subnetwork prediction model. This model significantly out-performed existing clinically-used molecular tests in an independent 1,742-patient validation cohort. SIMMS is generic and can work with any molecular data or biological network, and is freely available at:https://cran.r-project.org/web/packages/SIMMS. |
| Databáze: | OpenAIRE |
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