Biology subjects

Aziz, M. A.

Publications and source records attributed to Aziz, M. A..

5 recordsLinked to original sources

bioRxiv2024

DEEP LEARNING APPROACH FOR RENAL CELL CARCINOMA DETECTION,SUBTYPING, AND GRADING

We propose a comprehensive end-to-end pipeline designed for the detection, subtyping, and grading of tumors. Our proposed method-ology initiates the generation of a heat map, indicating the severity of the tumor. Subsequently, the identification of the most critical patches is conducted based on the probability scores. These identified patches are then directed to a grade prediction network. A distinctive aspect of our research lies in being the first to explore an end-to-end pipeline for both heat map generation and grading prediction. Our experiments were conducted leveraging the public, The Cancer Genome Atlas (TCGA) repository, focusing specifically on renal cancer. We introduced additional patch-level labels to improve the model performance. The generation of tumor heat maps targeted three primary cancer subtypes: clear cell, papillary, and chromophobe. To enhance our approach, we implemented center-loss and introduced a method aimed at refining the quality of patches. The experimental outcomes highlight superior performance compared to state-of-the-art method. This research contributes to the advancement of tumor detection and grading, emphasizing the significance of an integrated approach for heat map generation and grading pre-diction.

bioinformatics↗

bioRxiv2023

Genome-Wide Exploration of the Opportunistic Providencia stuartii Unveils the Novel Genetic Interactions with the Virulence Gene of Diarrheal Pathogens

Diarrhea typically indicates an intestinal disorder, which can occur from viruses, parasites or bacterial infection. Along with the common diarrhea-causing pathogens, opportunistic bacteria may also play a role in the etiology of diarrheal disease. One of the opportunists bacteria that can cause diarrhea in both children and adults is Providencia stuartii. Therefore, the goal of this study is to explore the genetic mechanism of the opportunistic P. stuartii in microbial interactions with common diarrheal pathogens. Hence, P. stuartii was identified by utilizing the morphological observation and molecular techniques. Afterwards, the entire genome of P. stuartii was sequenced, assembled and annotated to explore the genomic insights. In addition, the virulence genes of 100 whole genome sequences from ten prevalent diarrhea-causing bacteria were identified and prioritized. Finally, the system biology approach was used to predict the protein-protein interaction network between P. stuartii and the virulence genes. The results of the present study suggests that complete genome sequencing of this bacteria contains 4011 proteins, which are crucial for this bacterium to survive. Additionally, 16 gene clusters provide 207 interacting genes that could interact with biological and molecular function, subcellular localization and pathway. The microbial interaction accompanying the virulence gene was found in all 10 diarrhea-causing bacteria except Clostridium difficile. These findings of this study could aid in the exploration of Providencia stuartii as the major causative agent of diarrhea. Additionally, the pathophysiology of diarrhea can be investigated using the microbial interactions between P. stuartii and the typical diarrheal bacteria. The results of this study may therefore be used to determine the most effective therapeutic targets for the development of medications to treat diarrhea.

genomics↗

bioRxiv2022

Timing and magnitude of the type-I interferon response are determinants of disease tolerance in arbovirus infection

Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: (i) "resistance", directed to abrogate virus replication, or (ii) "disease tolerance", aimed to avoid organ and tissue damage without overly controlling viral burden. The overall principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of a major disease of ruminants, bluetongue, as a model system to investigate the mechanisms of disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Here, we show that BTV consistently reaches higher titres in ovine primary cells, compared to cells derived from cattle. The variable replication kinetics of BTV in sheep and cattle cells were mostly abolished by abrogating the cell type-I interferon (IFN) response. By screening a library of bovine interferon stimulated genes (ISGs), we identified restriction factors blocking BTV replication, however both sheep and cattle orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells, compared to cattle cells, which results in an earlier downregulation of antiviral proteins. Moreover, by RNAseq we also show a more pronounced expression of ISGs in BTV infected cattle cells compared to sheep cells. Our data provide a new perspective on how the type-I IFN response in reservoir species can have overall positive effects on both virus and host evolution.

microbiology↗

bioRxiv2021

The Interferon Resistance of Transmitted HIV-1 is a Consequence of Enhanced Replicative Fitness

HIV-1 transmission via sexual exposure is a relatively inefficient process. When successful transmission does occur, newly infected individuals are colonized by either a single or a very small number of establishing virion(s). These transmitted founder (TF) viruses are more interferon (IFN) resistant than chronic control (CC) viruses present 6 months after transmission. To identify the specific molecular defences that make CC viruses more susceptible to the IFN-induced antiviral state than TF viruses, we established a pair of fluorescent GFP-IRES-Nef TF and CC viruses and used arrayed interferon-stimulated gene (ISG) expression screening. The relatively uniform ISG resistance of transmitted HIV-1 directed us to investigate the underlying mechanism. Our subsequent in silico simulations, modelling, and in vitro characterisation of a model TF/CC pair (closely matched in replicative fitness), revealed that small differences in replicative growth rates can explain the broad IFN resistance displayed by transmitted HIV-1. We propose that the apparent IFN resistance of transmitted HIV-1 is a consequence of enhanced replicative fitness, as opposed to specific resistance to individual IFN-induced defences.

microbiology↗

bioRxiv2019

TRIM69 inhibits Vesicular Stomatitis Indiana Virus (VSIV)

Vesicular Stomatitis Indiana Virus (VSIV) is a model virus that is exceptionally sensitive to the inhibitory action of interferons. Interferons induce an antiviral state by stimulating the expression of hundreds of interferon stimulated genes (ISGs). These ISGs constrain viral replication, limit tissue tropism, reduce pathogenicity and inhibit viral transmission. Because VSIV is used as a backbone for multiple oncolytic and vaccine strategies, understanding how ISGs restrict VSIV, not only helps in understanding VSIV-pathogenesis, but helps evaluate and understand the safety and efficacy of VSIV-based therapies. Thus there is a need to identify and characterize the ISGs that possess anti-VSIV activity. Using arrayed ISG expression screening, we identified TRIM69 as an ISG that potently inhibits VSIV. This inhibition was highly specific as multiple viruses (including influenza A virus, HIV-1, Rift Valley Fever Virus and dengue virus) were not affected by TRIM69. Indeed, just one amino acid substitution in VSIV can govern sensitivity/resistance to TRIM69. TRIM69 is highly divergent in human populations and exhibits signatures of positive selection that are consistent with this gene playing a key role in antiviral immunity. We propose that TRIM69 is an IFN-induced inhibitor of VSIV and speculate that TRIM69 could be important in limiting VSIV pathogenesis and might influence the specificity and/or efficacy of vesiculovirus-based therapies.\n\nIMPORTANCEVesicular Stomatitis Indiana Virus (VSIV) is a veterinary pathogen that is also used as a backbone for many oncolytic and vaccine strategies. In natural and therapeutic settings, VSIV infection is sensed by the host and host-cells make proteins that protect them from viruses. In the case of VSIV, these antiviral proteins constrain viral replication and protect most healthy tissues from virus infection. In order to understand how VSIV causes disease and how healthy tissues are protected from VSIV-based therapies, it is crucial that we identify the proteins that inhibit VSIV. Here we show that TRIM69 is an antiviral defence that can potently and specifically block VSIV infection.

microbiology↗