A deep learning approach to identify gene targets of a therapeutic for human splicing disorders

Autor: Dadi Gao, Elisabetta Morini, Monica Salani, Aram J. Krauson, Anil Chekuri, Neeraj Sharma, Ashok Ragavendran, Serkan Erdin, Emily M. Logan, Wencheng Li, Amal Dakka, Jana Narasimhan, Xin Zhao, Nikolai Naryshkin, Christopher R. Trotta, Kerstin A. Effenberger, Matthew G. Woll, Vijayalakshmi Gabbeta, Gary Karp, Yong Yu, Graham Johnson, William D. Paquette, Garry R. Cutting, Michael E. Talkowski, Susan A. Slaugenhaupt

Publikováno v: Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)

Drugs that modify RNA splicing are promising treatments for many genetic diseases. Here the authors show that deep learning strategies can predict drug targets, strongly supporting the use of in silico approaches to expand the therapeutic potential o

Externí odkaz: https://doaj.org/article/a1488d5827774183bb159243db93b815

Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia

Autor: Anil Chekuri, Emily M Logan, Aram J Krauson, Monica Salani, Sophie Ackerman, Emily G Kirchner, Jessica M Bolduc, Xia Wang, Paula Dietrich, Ioannis Dragatsis, Luk H Vandenberghe, Susan A Slaugenhaupt, Elisabetta Morini

Publikováno v: Human Molecular Genetics. 31:1776-1787

Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease caused by a splicing mutation in the gene encoding Elongator complex protein 1 (ELP1, also known as IKBKAP). This mutation results in tissue-specific skipping of exon 20 w

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a1d060bbef9c4231da011ade6e229d0
https://doi.org/10.1093/hmg/ddab359

Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage

Autor: Elisabetta Morini, Dadi Gao, Emily M. Logan, Monica Salani, Aram J. Krauson, Anil Chekuri, Yei-Tsung Chen, Ashok Ragavendran, Probir Chakravarty, Serkan Erdin, Alexei Stortchevoi, Jesper Q. Svejstrup, Michael E. Talkowski, Susan A. Slaugenhaupt

Publikováno v: Morini, E, Gao, D, Logan, E M, Salani, M, Krauson, A J, Chekuri, A, Chen, Y T, Ragavendran, A, Chakravarty, P, Erdin, S, Stortchevoi, A, Svejstrup, J Q, Talkowski, M E & Slaugenhaupt, S A 2022, ' Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage ', Journal of Genetics and Genomics, vol. 49, no. 7, pp. 654-665 . https://doi.org/10.1016/j.jgg.2021.11.011
J Genet Genomics

Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1 (ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::341ff35a7aab7989d09801673cb24a37

Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia

Autor: Elisabetta Morini, Ackerman S, Bolduc Jm, Xia Wang, Susan A. Slaugenhaupt, Aram J. Krauson, Luk H. Vandenberghe, Anil Kumar Chekuri, Ioannis Dragatsis, Kirchner Eg, Monica Salani, Paula Dietrich, Emily M. Logan

Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease caused by a splicing mutation in the gene encoding Elongator complex protein 1 (ELP1, also known asIKBKAP). This mutation results in tissue-specific skipping of exon 20 wi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::441dc2f404f3fabcc0e54d8012b36a3a
https://doi.org/10.1101/2021.06.04.447086

A deep learning approach to identify new gene targets of a novel therapeutic for human splicing disorders

Autor: Emily M. Logan, Dadi Gao, Graham Johnson, Elisabetta Morini, Serkan Erdin, Nikolai Naryshkin, Susan A. Slaugenhaupt, Kerstin Effenberger, Matt Woll, Amal Dakka, Michael E. Talkowski, Vijayalakshmi Gabbeta, Ashok Ragavendran, Wencheng Li, Monica Salani, Gary Mitchell Karp, Anil Kumar Chekuri, Aram J. Krauson, William D. Paquette, Yong Yu, Chris Trotta

Pre-mRNA splicing is a key control point in human gene expression. Disturbances in splicing due to mutation or aberrant splicing regulatory networks lead to dysregulated protein expression and contribute to a substantial fraction of human disease. Se

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::921ae3edfae1c7d1d9e1eba7991015cd