• SyncroPatch 384/768i

    APC with highest throughput on the market
  • SyncroPatch 384/768i

    384 cells in parallel => upgradable to 768
  • SyncroPatch 384/768i

    True HTS AND Gigaohm seals
  • SyncroPatch 384/768i

    Analysis Software even more powerful than before
  • SyncroPatch 384/768i

    Assay flexibility via high tech

2019 - Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium

icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Pre-publication in bioRxiv Biology (2019)

Authors:
Heyne H.O., Baez-Nieto D., Iqbal S., Palmer D., Brunklaus A., Johannesen K.M., Lauxmann S., Lemke J.R., Møller R.S., Pérez-Palma E., Scholl U., Syrbe S., Lerche H., May P., Lal D., Campbell A.J., Pan J., Wang H.-R., Daly M.J.

Preprint Source:
bioRxiv (2019) doi: org/10.1101/637041


Abstract:

Malfunctions of voltage-gated sodium and calcium channels (SCN and CACNA1 genes) have been associated with severe neurologic, psychiatric, cardiac and other diseases. Altered channel activity is frequently grouped into gain or loss of ion channel function (GOF or LOF, respectively) which is not only corresponding to clinical disease manifestations, but also to differences in drug response. Experimental studies of channel function are therefore important, but laborious and usually focus only on a few variants at a time. Based on known gene-disease-mechanisms, we here infer LOF (518 variants) and GOF (309 variants) of likely pathogenic variants from disease phenotypes of variant carriers. We show regional clustering of inferred GOF and LOF variants, respectively, across the alignment of the entire gene family, suggesting shared pathomechanisms in the SCN/CACNA1 genes. By training a machine learning model on sequence- and structure-based features we predict LOF- or GOF- associated disease phenotypes (ROC = 0.85) of likely pathogenic missense variants. We then successfully validate the GOF versus LOF prediction on 87 functionally tested variants in SCN1/2/8A and CACNA1I (ROC = 0.73) and in exome-wide data from > 100.000 cases and controls. Ultimately, functional prediction of missense variants in clinically relevant genes will facilitate precision medicine in clinical practice.


Download here

Back to Overview

SyncroPatch 384i brochure

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.