Biology subjects

Yusuf, I.

Publications and source records attributed to Yusuf, I..

4 recordsLinked to original sources

bioRxiv2024

CoPPIs Algorithm: A Tool to Unravel Protein Cooperative Strategies in Pathophysiological Conditions

We present here the Co-expressed Protein-Protein Interactions (CoPPIs) algorithm. In addition to minimizing correlation-causality imbalance and contextualizing PPIs to the investigated systems, it combines PPIs and protein co-expression networks to identify differentially correlated functional modules. To test CoPPIs, we processed a set of proteomic profiles from different brain areas of controls and subjects affected by idiopathic Parkinsons disease or carrying a GBA1 mutation. Its robustness was supported by the extraction of functional modules, related to translation and mitochondria, whose involvement in PD pathogenesis is well documented. Furthermore, the selection of hubs and bottlenecks from the weighted PPI networks provided molecular clues consistent with the PD pathophysiology. Of note, like quantification, the CoPPIs algorithm revealed less variations when comparing disease groups than when comparing diseased and controls. However, correlation and quantification results showed low overlap, suggesting the complementarity of these measures. An observation that opens the way to a new investigation strategy that takes into account not only protein expression, but also the level of coordination among proteins that cooperate to perform a given function.

systems biology↗

bioRxiv2024

RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability

TDP43 is an RNA/DNA binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to the formation of detrimental cytosolic aggregates and a reduction in nuclear functionality within neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expressions. Here, we show that TDP43 depletion or overexpression directly affects the expression of key MMR genes. Alterations include MLH1, MSH2, MSH3, MSH6, and PMS2 levels across various primary cell lines, independent of their proliferative status. Our results specifically establish that TDP43 selectively influences the expression of MLH1 and MSH6 by influencing their alternative transcript splicing patterns and stability. We furthermore find aberrant MMR gene expression is linked to TDP43 proteinopathy in two distinct ALS mouse models and post-mortem brain and spinal cord tissues of ALS patients. Notably, MMR depletion resulted in the partial rescue of TDP43 proteinopathy-induced DNA damage and signaling. Moreover, bioinformatics analysis of the TCGA cancer database reveals significant associations between TDP43 expression, MMR gene expression, and mutational burden across multiple cancers. Collectively, our findings implicate TDP43 as a critical regulator of the MMR pathway and unveil its broad impact on the etiology of both neurodegenerative and neoplastic pathologies.

biochemistry↗

bioRxiv2023

Oncolytic Newcastle disease virus enhanced apoptosis in colorectal cancer cell lines

Colorectal cancer (CRC) is a deadly disease with a high prevalence and mortality rate worldwide. Previous investigations have shown that Newcastle disease virus (NDV) exhibits oncolytic activity and antitumor immunostimulation properties on several types of tumor cells but not normal cells. This study aims to examine NDV oncolytic activity against two kinds of human CRC cell lines, i.e., HCT116 and SW620, as well as its ability to induce apoptosis. The results showed that CRC cell lines were susceptible to NDV LaSota strain and the mechanism of death was due to caspase-dependent pathways apoptosis, followed by interferon signaling competence. NDV-induced proinflammatory cytokines in CRC cells might have contributed to apoptosis mechanism. Therefore, further investigation is recommended, using the findings obtained in this study as a basis for an animal CRC model.

immunology↗

bioRxiv2019

Genetic Risk Factors for Colorectal Cancer in Multiethnic Indonesians

PurposeColorectal cancer is a common cancer in Indonesia, yet it has been understudied. We conduct a genome-wide association study focused on evaluation and discovery of colorectal cancer risk factors in Indonesians.\n\nMethodsWe administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique.\n\nResultsWe replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk.\n\nConclusionsThis work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

genomics↗