Biology subjects

Shehwana, H.

Publications and source records attributed to Shehwana, H..

3 recordsLinked to original sources

bioRxiv2021

TISON: a next-generation multi-scale modeling theatre for in silico systems oncology

Multi-scale models integrating biomolecular data from genetic, transcriptional, and translational levels, coupled with extracellular microenvironments can assist in decoding the complex mechanisms underlying system-level diseases such as cancer. To investigate the emergent properties and clinical translation of such cancer models, we present Theatre for in silico Systems Oncology (TISON, https://tison.lums.edu.pk), a next-generation web-based multi-scale modeling and simulation platform for in silico systems oncology. TISON provides a "zero-code" environment for multi-scale model development by seamlessly coupling scale-specific information from biomolecular networks, microenvironments, cell decision circuits, in silico cell lines, and organoid geometries. To compute the temporal evolution of multi-scale models, a simulation engine and data analysis features are also provided. Furthermore, TISON integrates patient-specific gene expression data to evaluate patient-centric models towards personalized therapeutics. Several literature-based case studies have been developed to exemplify and validate TISONs modeling and analysis capabilities. TISON provides a cutting-edge multi-scale modeling pipeline for scale-specific as well as integrative systems oncology that can assist in drug target discovery, repositioning, and development of personalized therapeutics.

systems biology↗

bioRxiv2020

ace2 expression is higher in intestines and liver while being tightly regulated in development and disease in zebrafish

Human Angiotensin I Converting Enzyme 2 (ACE2) that acts as a receptor for SARS-CoV-2 entry is highly expressed in human type II pneumocytes and enterocytes and similarly in other mammals and zebrafish (Danio rerio). The zebrafish genome has a highly conserved, one-to-one ortholog of ACE2, i.e., ace2, whose expression profile however has not yet been studied during development or in pathologies relevant to COVID-19. Herein, we identified significant development-, tissue- and gender-specific modulations in ace2 expression based on meta-analysis of zebrafish Affymetrix transcriptomics datasets (ndatasets=107, GPL1319 in GEO database). Co-expression network analysis of ace2 revealed distinct positively correlated (carboxypeptidase activity and fibrin clot formation), and negatively correlated (cilia biogenesis/transport and chromatin modifications) STRING network modules. Using additional transcriptomics datasets, we showed zebrafish embryos before 3 days post fertilization (dpf) exhibited low levels of ace2 that increased significantly until 4 dpf implicating a role for ace2 in organogenesis. Re-analysis of RNA-seq datasets from zebrafish adult tissues demonstrated ace2 was expressed highly in intestines, variably in liver, and at lower levels in other organs. In addition, zebrafish females and males showed significant dimorphism in their age-dependent expression of ace2, and between ovary and testis where the latter had higher levels. Moreover, we demonstrated ace2 expression was significantly modulated under different physiological and pathological conditions associated with development, diet, infection, and inflammation. Our findings implicate a novel translational role for zebrafish ace2 in differentiation and pathologies predominantly found in intestines and liver, in which the effects of SARS-CoV-2 could be detrimental.

molecular biology↗

bioRxiv2020

Transcription Factors STAT5A and SPI1 Reveals RHBDD2 as a Potential Biomarker in Sepsis and Septic Shock

Sepsis is a serious health situation caused by uncontrolled infection and septic shock is a severe condition of sepsis. RHBDD2 is a member of the rhomboid superfamily which is overexpressed in different types of cancer and associated with ER stress and estrogen receptor. Using microarray gene expression data and using different computational techniques this study investigated the role of RHBDD2 in sepsis and septic shock. Finds functional annotation of RHBDD2 using co-expression analysis and identified the deregulation of RHBDD2 in sepsis using differential expression analysis. Results show that RHBDD2 is overexpressed in sepsis and septic shock. The GO enrichment analysis, KEGG pathways, and biological functions of the RHBDD2 co-expressed genes module show that it is involved in most of the sepsis-related biological functions and also plays a role in most of the infection-related pathways which lead to sepsis and septic shock. RHBDD2 is regulated by STAT5A and SPI1 transcription factors in sepsis and septic shock. The identification of the RHBDD2 as a biomarker may facilitate in septic shock diagnosis, treatment, and prognosis.

bioinformatics↗