bioRxiv Science⌕ Search

Biology subjects

Rashid, M. M.

Publications and source records attributed to Rashid, M. M..

6 recordsLinked to original sources

Platform Biological Divergence: quantifying gene-level differences between bulk and single-cell transcriptomics in breast cancer

Bulk and single-cell RNA-seq offer complementary views of tissue transcriptomes. Nevertheless, pseudo-bulk (PB) profiles derived from single-cell data often differ systematically from true bulk measurements. These discrepancies are rarely quantified at the gene level, despite their impact on downstream analyses. To investigate the PB-bulk disagreement, here we introduce, based on linear mixture models, a gene-centric platform biological divergence (PBD) score. Across matched breast cancer, human adipose, and healthy retinal datasets, PBD stratifies genes into low-PBD "stable proxies" that retain true biological signals and high-PBD "divergent drivers" that shape PB-bulk differences. High-PBD (15-25%) genes show platform-specific signatures: bulk-enriched drivers highlight stromal, immune, and metabolic programs (breast cancer, adipose) and housekeeping/translational pathways (retina), whereas PB-enriched drivers reflect cell-intrinsic and regulatory processes, including immune, endothelial, progenitor, ECM, developmental, and photoreceptor programs. In contrast, low-PBD genes reliably preserve biology-driven variation and improve cross-platform concordance. Overall, the PBD framework reveals systematic gene-level biases between PB and bulk profiles, enabling more accurate comparison and integration of bulk and single-cell transcriptomes across tissues and disease contexts.

bioinformatics↗

Machine learning differentiates between bulk and pseudo-bulk RNA-seq datasets

Modern synthetic data generators and deconvolution methods rely heavily on single-cell (sc) RNA- seq data. Aggregated scRNA-seq (pseudo-bulk) is commonly assumed to closely match true bulk RNA-seq, making it a dependable benchmark for developing and evaluating new bioinformatics methods. Here, we investigated paired bulk and scRNA-seq datasets using machine learning techniques to assess the fidelity of pseudo-bulk profiles. Our results demonstrate that pseudo-bulks differ substantially from bulk RNA-seq in both analytic metrics and biological processes.

bioinformatics↗

Electrical charge-mediated transformation for efficient plant genome editing

Genome editing technologies possess significant potential to enhance plant breeding; however, the delivery of editing constructs poses challenges in numerous crop species due to their resistance to transformation or tissue culture. This study introduces an innovative approach for the delivery of ribonucleoprotein (RNP) complexes and plasmid vectors into intact, regenerable faba bean plant tissues. This is accomplished by applying an electric current that makes plant cell walls and membranes permeable, thereby allowing the entry of macromolecular constructs into the cell and nucleus. This study assessed the efficacy of electric pulse-mediated transfection in faba bean by generating stable GFP-expressing faba bean plants. Furthermore, we incorporated it into faba bean leaf tissue and demonstrated its application in both embryos and leaf tissues. We demonstrate DNA-free genome editing by targeting the endogenous phytoene desaturase gene (PDS), achieving a mutation success rate of 50%. This method is efficient and economical, necessitating limited technical training. It is applicable to both leaf and embryo tissues, thereby enhancing its utility for crop improvement. This technique shows potential for the development of new crop varieties that can more effectively address global climate challenges.

plant biology↗

The main duct of von Ebner's glands is a source of Sox10+ taste bud progenitors and susceptible to pathogen infections

We have recently demonstrated that Sox10-expressing (Sox10+) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing Sox10+ cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebners glands (vEGs) that are connected to the trench of circumvallate and foliate papillae. In this study, we used inducible Cre mouse models to map the cell lineages of connective tissue (including stromal and Schwann cells) and vEGs and performed single cell RNA-sequencing of the epithelium of Sox10-Cre/tdT mouse circumvallate/vEG complex. In vivo lineage mapping showed that the distribution of traced cells in circumvallate taste buds was closely linked with that in the vEGs, but not in the connective tissue. Sox10, but not the known stem cells marker Lgr5, expression was enriched in the cell clusters of main ducts of vEGs that contained abundant proliferating cells, while Sox10-Cre/tdT expression was enriched in type-III taste bud cells and excretory ductal cells. Moreover, multiple genes encoding pathogen receptors are enriched in the vEG main ducts. Our data indicate that the main duct of vEGs is a source of Sox10+ taste bud progenitors and susceptible to pathogen infections.

cell biology↗

Phage predation and antibiotic exposure are inversely associated with disease severity and shape pathogen genetic diversity in cholera patients

Despite an increasingly detailed picture of the molecular mechanisms of phage-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. Here we report a year-long, nation-wide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative PCR, while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of anti-phage defenses, predation was effective, with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of anti-phage defenses, predation was ineffective, with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics. One Sentence SummaryA survey of cholera patients in Bangladesh identifies phage predation as a biomarker of disease severity and driver of coevolution within patients.

microbiology↗

Exploring of bacterial blight resistance in landraces, mining of resistant gene(s) and genetic divergence of resistant germplasm through molecular markers and quantitative traits.

Bacterial blight, one of the oldest and severe diseases of rice poses a major threat towards global rice production and food security. Thereafter, sustainable management of this disease has given paramount importance globally. In the current study, we explored 792 landraces to evaluate their disease reaction status against three highly virulent strains (BXo69, BXo87 and BXo93) of Xanthomonas oryzae pv. oryzae (Xoo). Subsequently, we intended to identify the possible candidate resistant (R) genes responsible for the resistant reaction using six STS markers correspond to Xa4, xa5, Xa7, xa13, Xa21 and Xa23 genes and finally, we evaluated morphological and molecular diversity of the potential bacterial blight resistant germplasm using quantitative traits and ISSR markers. Based on pathogenicity test, a single germplasm was found as highly resistant while, 33 germplasm were resistant and 40 were moderately resistant. Further molecular study on these 74 germplasm divulged that 41 germplasm carried Xa4 gene, 15 carried xa5 gene, 62 carried Xa7 gene, 33 carried xa13 gene, and 19 carried Xa23 gene. Only a single germplasm consisted of Xa21 gene. Interestingly, we found a wide range of gene combinations ranged from 2 to 4 genes among the germplasm resistant to bacterial blight and G3 genotype (Acc. No. 4216; highly resistant) having Xa4, Xa7, xa13, Xa21 and G43 genotype (Acc. No. 1523; resistant) having Xa4, xa5, xa13 and Xa23 gene combination being the most effective against all the Xoo strains. Nonetheless, UPGMA dendrogram and heatmap analysis based on quantitative traits identified two important clusters viz. cluster-III and cluster-VIII with multiple desired traits However, genetic similarity based on ISSR marker data pointed out 3 germplasm, namely, G20 (Acc. No. 4004; contained Xa4, Xa7, xa13 genes), G17 (Acc. No. 3981; contained Xa7, xa13 genes) and G6 (Acc. No. 991; contained Xa4, Xa7, xa13, Xa23 genes) having comparatively lower genetic similarity (0.30, 0.37 and 0.38, respectively) with elite variety BRRI dhan28. Notably, Mantle test of molecular and morphological data indicated that there was a positive correlation (r = 0.113) between them. The outcome of this study would enrich and diversify the rice gene pool and would be useful for the development of durable bacterial blight resistant varieties.

plant biology↗