SearcharxivSearch

arXiv subjects

Lana Garmire

Publications and source records attributed to Lana Garmire.

2 recordsLinked to original sources

BSNMani: Bayesian Scalar-on-network Regression with Manifold Learning

Brain connectivity analysis is crucial for understanding brain structure and neurological function, shedding light on the mechanisms of mental illness. To study the association between individual brain connectivity networks and the clinical characteristics, we develop BSNMani: a Bayesian scalar-on-network regression model with manifold learning. BSNMani comprises two components: the network manifold learning model for brain connectivity networks, which extracts shared connectivity structures and subject-specific network features, and the joint predictive model for clinical outcomes, which studies the association between clinical phenotypes and subject-specific network features while adjusting for potential confounding covariates. For posterior computation, we develop a novel two-stage hybrid algorithm combining Metropolis-Adjusted Langevin Algorithm (MALA) and Gibbs sampling. Our method is not only able to extract meaningful subnetwork features that reveal shared connectivity patterns, but can also reveal their association with clinical phenotypes, further enabling clinical outcome prediction. We demonstrate our method through simulations and through its application to real resting-state fMRI data from a study focusing on Major Depressive Disorder (MDD). Our approach sheds light on the intricate interplay between brain connectivity and clinical features, offering insights that can contribute to our understanding of psychiatric and neurological disorders, as well as mental health.

stat.ME

Prediction of repurposed drugs for treating lung injury in COVID-19

Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, brought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Inhibition of Angiotensin-converting enzyme 2 (ACE2) caused by spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 inhibitor and in human COVID-19 patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues, including signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA. It also uniquely targets genes related to lung injury, such as CALR and MMP14. In summary, this study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.

q-bio.TO