Biology subjects

Bashir, M.

Publications and source records attributed to Bashir, M..

3 recordsLinked to original sources

bioRxiv2024

Machine learning reveals novel targets for both glioblastoma and osteosarcoma

Glioblastoma and osteosarcoma originate from the same lineage, yet patients with these two tumour types show significant differences in survival outcomes. Transcriptomic analysis comparing these tumours reveals that over 65% genes show similar expression patterns. Principal component analysis further demonstrates substantial similarities between these two tumour types, albeit with discernible differences. Deep learning analysis employing an autoencoder unveils nuanced distinctions and similarities of these two tumours at a high resolution. A classification model, leveraging gradient boosting with eXtreme Gradient Boosting (XGBoost), achieves high accuracy in distinguishing between these two tumour types. Identification of key contributors to the models performance is facilitated by SHapley Additive exPlanations (SHAP), yielding two lists of top target genes with and without considering gender. Notably, these SHAP targets tend to cluster within one or two networks of signalling pathways. Remarkably, gene expression levels of many of these SHAP targets alone can recapitulate survival differences solely based on clinical data between glioblastoma and osteosarcoma patients. Of particular interest, C2ORF72 emerges as a common target from both lists, representing an uncharacterised protein with promising potential as a novel target for diagnostic, prognostic, and therapeutic target for both glioblastoma and osteosarcoma.

genomics↗

bioRxiv2023

Lipidome unsaturation affects the morphology and proteome of the Drosophila eye.

While the proteome of an organism is largely determined by the genome, the lipidome is shaped by a poorly understood interplay of environmental factors and metabolic processes. To gain insights into the underlying mechanisms, we analyzed the impacts of dietary lipid manipulations on the ocular proteome of Drosophila melanogaster. We manipulated the lipidome with synthetic food media that differed in the supplementation of an equal amount of saturated or polyunsaturated triacylglycerols. This allowed us to generate flies whose eyes had a highly contrasting length and unsaturation of glycerophospholipids, the major lipid class of biological membranes, while the abundance of other membrane lipid classes remained unchanged. By bioinformatically comparing the resulting ocular proteomic trends and contrasting them with the impacts of vitamin A deficiency, we identified ocular proteins whose abundances are differentially affected by lipid saturation and unsaturation. For instance, we unexpectedly identified a group of proteins that have muscle-related functions and increase their abundances in the eye upon lipidome unsaturation but are unaffected by lipidome saturation. Moreover, we identified two differentially lipid-responsive proteins involved in stress responses, Turandot A and Smg5, whose abundances decrease with lipid unsaturation. Lastly, we discovered that the ocular lipid class composition is robust to dietary changes and propose that this may be a general homeostatic feature of the organization of eukaryotic tissues, while the length and unsaturation of fatty acid moieties is more variable to compensate environmental challenges. We anticipate that these insights into the molecular responses of the Drosophila eye proteome to specific lipid manipulations will guide the genetic dissection of the mechanisms that maintain visual function when the eye is exposed to dietary challenges.

neuroscience↗

bioRxiv2023

Eye proteome of Drosophila melanogaster

The Drosophila melanogaster eye is a popular model to elucidate the molecular mechanisms that underlie the structure and function of the eye as well as the causes of retinopathies. For instance, the Drosophila eye has been used to investigate the impacts of ageing and environmental stresses such as light-induced damage or dietary deficiencies. Moreover, large-scale screens have isolated genes whose mutation causes morphological and functional ocular defects, which includes key components of the phototransduction cascade. However, the proteome of the Drosophila eye is poorly characterized. Here, we used GeLC-MS/MS to quantify 3516 proteins he adult Drosophila melanogaster eye and provide a generic and expandable resource for further genetic, pharmacological, and dietary studies.

neuroscience↗