Predicting functional effects of missense variants in voltage-gated sodium and calcium channels

Author:

Heyne Henrike O.1234ORCID,Baez-Nieto David3ORCID,Iqbal Sumaiya1235ORCID,Palmer Duncan S.123ORCID,Brunklaus Andreas67ORCID,May Patrick8ORCID,Johannesen Katrine M.910ORCID,Lauxmann Stephan11ORCID,Lemke Johannes R.12ORCID,Møller Rikke S.910ORCID,Pérez-Palma Eduardo1314ORCID,Scholl Ute I.1516ORCID,Syrbe Steffen17ORCID,Lerche Holger11ORCID,Lal Dennis1231314,Campbell Arthur J.35ORCID,Wang Hao-Ran3ORCID,Pan Jen3,Daly Mark J.1234ORCID,

Affiliation:

1. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

3. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

4. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 5WR36M Helsinki, Finland.

5. Center for Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

6. Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow G51 4TF, UK.

7. School of Medicine, University of Glasgow, Glasgow G12 8QQ, UK.

8. Luxembourg Centre for Systems Biomedicine, Belvaux, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg.

9. Department of Epilepsy Genetics and Personalized Treatment, Danish Epilepsy Centre, 4293 Dianalund, Denmark.

10. Department of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.

11. Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany.

12. Institute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany.

13. Cologne Center for Genomics (CCG), University of Cologne, 50923, Germany.

14. Genomic Medicine Institute, Lemer Research Institute Cleveland Clinic, OH G92J47, USA.

15. Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care and BIH Center for Regenerative Therapies, 10178 Berlin, Germany.

16. Berlin Institute of Health (BIH), 10178 Berlin, Germany.

17. Division of Pediatric Epileptology, Center for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Abstract

A machine learning method can predict loss- versus gain-of-function effects of human genetic variants in disease-associated ion channels.

Funder

National Institute of Mental Health

National Human Genome Research Institute

National Institute of Neurological Disorders and Stroke

Simons Foundation

Deutsche Forschungsgemeinschaft

Bundesministerium für Bildung und Forschung

Horizon 2020

Stanley Foundation

Stiftung Charite

Dietmar Hopp Stiftung

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Reference133 articles.

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