AMELIE 2 speeds up Mendelian diagnosis by matching patient phenotype & genotype to primary literature
| Autor: | Harendra Guturu, Cole A. Deisseroth, Alexander Ratner, Ethan Steinberg, Peter D. Stenson, David N. Cooper, Maximilian Haeussler, Gill Bejerano, Karthik A. Jagadeesh, Christopher Ré, Alan H. Beggs, Mark Diekhans, Aaron M. Wenger, Jonathan A. Bernstein, Johannes Birgmeier |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Candidate gene Pediatrics medicine.medical_specialty Matching (statistics) Singleton business.industry Disease 3. Good health 03 medical and health sciences symbols.namesake 0302 clinical medicine Cohort Phenotype genotype Mendelian inheritance symbols Medicine business 030217 neurology & neurosurgery Exome sequencing 030304 developmental biology |
| Popis: | The diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication/s supporting a single gene that best explains a patient’s disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts, downloads and further parses hundreds of thousands of full text articles in search of information supporting the causality and associated phenotypes of any published genetic variant. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient’s given set of phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario. AMELIE ranked the causative gene at the very top in 2/3 of 215 diagnosed singleton Mendelian patients. Evaluating only the top 11 AMELIE scored genes of 127 (median) candidate genes per patient results in rapid diagnosis for 90+% of cases. AMELIE-based evaluation of all cases is 3-19x more efficient than hand-curated database-based approaches. We replicate these results on a cohort of clinical cases from Stanford Children’s Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface and code will be available at AMELIE.stanford.edu. A pilot run of the web portal has already served many thousands of job submissions from dozens of countries. |
| Databáze: | OpenAIRE |
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