Phenogenon: Gene to phenotype associations for rare genetic diseases.
As high-throughput sequencing is increasingly applied to the molecular diagnosis of rare Mendelian disorders, a large number of patients with diverse phenotypes have their genetic and phenotypic data pooled together to uncover new gene-phenotype relations. We introduce Phenogenon, a statistical tool...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0230587 |
| _version_ | 1818891759573270528 |
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| author | Nikolas Pontikos Cian Murphy Ismail Moghul Gavin Arno Kaoru Fujinami Yu Fujinami Dayyanah Sumodhee Susan Downes Andrew Webster Jing Yu UK Inherited Retinal Dystrophy Consortium, Phenopolis Consortium |
| author_facet | Nikolas Pontikos Cian Murphy Ismail Moghul Gavin Arno Kaoru Fujinami Yu Fujinami Dayyanah Sumodhee Susan Downes Andrew Webster Jing Yu UK Inherited Retinal Dystrophy Consortium, Phenopolis Consortium |
| author_sort | Nikolas Pontikos |
| collection | DOAJ |
| description | As high-throughput sequencing is increasingly applied to the molecular diagnosis of rare Mendelian disorders, a large number of patients with diverse phenotypes have their genetic and phenotypic data pooled together to uncover new gene-phenotype relations. We introduce Phenogenon, a statistical tool that combines, Human Phenotype Ontology (HPO) annotated patient phenotypes, gnomAD allele population frequency, and Combined Annotation Dependent Depletion (CADD) score for variant pathogenicity, in order to jointly predict the mode of inheritance and gene-phenotype associations. We ran Phenogenon on our cohort of 3,290 patients who had undergone whole exome sequencing. Among the top associations, we recapitulated previously known, such as "SRD5A3-Abnormal full-field electroretinogram-recessive" and "GRHL2 -Nail dystrophy-recessive", and discovered one potentially novel, "RRAGA-Abnormality of the skin-dominant". We also developed an interactive web interface available at https://phenogenon.phenopolis.org to visualise and explore the results. |
| first_indexed | 2024-12-19T17:45:55Z |
| format | Article |
| id | doaj.art-1983f04785234a82b57df50babe8728a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T17:45:55Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1983f04785234a82b57df50babe8728a2022-12-21T20:12:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01154e023058710.1371/journal.pone.0230587Phenogenon: Gene to phenotype associations for rare genetic diseases.Nikolas PontikosCian MurphyIsmail MoghulGavin ArnoKaoru FujinamiYu FujinamiDayyanah SumodheeSusan DownesAndrew WebsterJing YuUK Inherited Retinal Dystrophy Consortium, Phenopolis ConsortiumAs high-throughput sequencing is increasingly applied to the molecular diagnosis of rare Mendelian disorders, a large number of patients with diverse phenotypes have their genetic and phenotypic data pooled together to uncover new gene-phenotype relations. We introduce Phenogenon, a statistical tool that combines, Human Phenotype Ontology (HPO) annotated patient phenotypes, gnomAD allele population frequency, and Combined Annotation Dependent Depletion (CADD) score for variant pathogenicity, in order to jointly predict the mode of inheritance and gene-phenotype associations. We ran Phenogenon on our cohort of 3,290 patients who had undergone whole exome sequencing. Among the top associations, we recapitulated previously known, such as "SRD5A3-Abnormal full-field electroretinogram-recessive" and "GRHL2 -Nail dystrophy-recessive", and discovered one potentially novel, "RRAGA-Abnormality of the skin-dominant". We also developed an interactive web interface available at https://phenogenon.phenopolis.org to visualise and explore the results.https://doi.org/10.1371/journal.pone.0230587 |
| spellingShingle | Nikolas Pontikos Cian Murphy Ismail Moghul Gavin Arno Kaoru Fujinami Yu Fujinami Dayyanah Sumodhee Susan Downes Andrew Webster Jing Yu UK Inherited Retinal Dystrophy Consortium, Phenopolis Consortium Phenogenon: Gene to phenotype associations for rare genetic diseases. PLoS ONE |
| title | Phenogenon: Gene to phenotype associations for rare genetic diseases. |
| title_full | Phenogenon: Gene to phenotype associations for rare genetic diseases. |
| title_fullStr | Phenogenon: Gene to phenotype associations for rare genetic diseases. |
| title_full_unstemmed | Phenogenon: Gene to phenotype associations for rare genetic diseases. |
| title_short | Phenogenon: Gene to phenotype associations for rare genetic diseases. |
| title_sort | phenogenon gene to phenotype associations for rare genetic diseases |
| url | https://doi.org/10.1371/journal.pone.0230587 |
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