Toxicogenomic identification of repositioned therapy for a monogenic disease
Kort, E. J.; Sayed, N.; Liu, C.; Wu, S. M.; Wu, J. C.; Jovinge, S.
Show abstract
The cost of drug development from initial concept to FDA approval has been estimated to be about 2.6 billion USD.1 This cost precludes development of targeted therapies for rare diseases such as monogenetic cardiomyopathies. As part of the Library of Integrated Network-based Cellular Signatures (LINCS) program funded by the NIH, the Broad Institute of MIT has publicly released transcriptional profiles quantifying the effects of more than 25,000 perturbagens on the expression of 978 genes in up to 77 cell lines.2 Transcriptomics has been shown to be a powerful tool in repurposing drugs3,4 and this dataset affords us the unique opportunity to systematically identify small molecule mimics or inhibitors of specific genes, thereby identifying novel treatments for genetic disorders. In this report, we take this approach to identify a novel drug therapy for a monogenic form of familial dilated cardiomyopathy with the transcriptional profile of FDA approved drugs. This approach could potentially be replicated for a wide range of monogenic diseases.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- S100A1ct: a synthetic peptide derived from human S100A1 protein improves cardiac contractile performance and survival in pre-clinical heart failure models 93%
- Defective Desmosomal Adhesion Causes Arrhythmogenic Cardiomyopathy by involving an Integrin-αVβ6/TGF-β Signaling Cascade 93%
- Transcriptional and Cellular Diversity of the Human Heart 92%
Similar papers in this journal
- Whole-genome sequencing analysis of clozapine-induced myocarditis 91%
- Investigating an in-silico approach for prioritizing antidepressant drug prescription based on drug-induced expression profiles and predicted gene expression 89%
- New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin 88%
Similar papers in this journal
- Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes 94%
- SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation 93%
- Development of Small Molecule MEIS Inhibitors that modulate HSC activity 93%
Similar papers in this journal
- Screening for variable drug responses using human iPSC cohorts 92%
- Identification of small molecule agonists of fetal hemoglobin expression for the treatment of sickle cell disease 91%
- Impaired Therapeutic Efficacy of Bone Marrow Cells from Post-Myocardial Infarction Patients in the TIME and LateTIME Clinical Trials 91%
Similar papers in this journal
- Investigation of genomic and transcriptomic risk factors in clopidogrel response in African Americans 92%
- SLCO1B1 functional variants and statin-induced myopathy in people with recent genealogical ancestors from Africa: a population-based real-world study 90%
- DrugWAS: Leveraging drug-wide association studies to facilitate drug repurposing for COVID-19 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.