Biology subjects

Umar, M.

Publications and source records attributed to Umar, M..

8 recordsLinked to original sources

bioRxiv2026

scRepresenter: a workflow for computing, integrating and benchmarking cellular representations in single-cell transcriptomics

MotivationSingle-cell RNA sequencing (scRNA-seq) has become an attractive tool for studying complex diseases, in which transient cell states affecting diverse cell populations characterise disease development and progression. However, due to data sparsity and disease heterogeneity analysis is often challenging. With recent advances in machine learning, two widely used approaches have emerged for learning cellular representations: large-scale foundation models and biological knowledge-guided methods. Despite their complementary strengths, there is currently no unified workflow for systematically comparing and integrating these approaches. ResultsHere, we present scRepresenter, an open-source workflow for computing, integrating, and validating cellular embeddings derived from foundation models and biological knowledge-guided methods in the context of complex diseases. It consists of two components: a command-line workflow that computes cellular embeddings and performs downstream analyses, and an interactive Shiny application for visualizing and comparing the computed embeddings. scRepresenter supports four categories of cellular representations: (1) expression-based, (2) knowledge-guided, (3) foundation model-derived, and (4) hybrid embeddings that combine foundation model-derived representations with knowledge-guided representations. This approach takes a cell-by-gene count matrix as input and outputs an integrated object containing the computed embeddings. Then, this object can be uploaded into our interactive Shiny application to compare different embeddings. AvailabilityThe workflow is available at https://github.com/GuilhermePocas/scRepresenter ContactAL291@cam.ac.uk; MA2129@cam.ac.uk

bioinformatics↗

bioRxiv2025

The tectum transversum(TTR) maintains patency of the developing coronal suture

Craniosynostosis is a congenital defect characterized by the premature fusion of calvarial bones, often attributed to the loss of fibrous sutures or deregulated bone formation. Recent studies have reported abnormal cartilage formation in multiple synostosis models, suggesting a potential role for cartilage in suture formation and maintenance. The tectum transversum (TTR) is a transient cartilage located between the coronal suture and dura, adjacent to the frontal and parietal bones. Abnormal TTR formation has been observed in several models; however, its role in coronal suture development remains unclear. In this study, we investigated the developmental process of TTR in a mouse model and characterized its formation in relation to adjacent tissues, including the calvarial bones and the coronal suture. Through genetic ablation of TTR, we demonstrated its essential role in maintaining coronal suture patency. Furthermore, spatial transcriptomics data suggest that TTR may function as a barrier to BMP signaling activation in the coronal suture, a process potentially influenced by the dura. These findings provide new insights into the mechanisms regulating coronal suture development and the etiology of coronal synostosis.

developmental biology↗

bioRxiv2024

Bounding phenotype transition probabilities via conditional complexity

By linking genetic sequences to phenotypic traits, genotype-phenotype maps represent a key layer in biological organisation. Their structure modulates the effects of genetic mutations which can contribute to shaping evolutionary outcomes. Recent work based on algorithmic information theory introduced an upper bound on the likelihood of a random genetic mutation causing a transition between two phenotypes, using only the conditional complexity between them. Here we evaluate how well this bound works for a range of genotype-phenotype maps, including a differential equation model for circadian rhythm, a matrix-multiplication model of gene regulatory networks, a developmental model of tooth morphologies for ringed seals, a polyomino-tile shape model of biological self-assembly, and the HP lattice protein model. By assessing three levels of predictive performance, we find that the bound provides meaningful estimates of phenotype transition probabilities across these complex systems. These results suggest that transition probabilities can be predicted to some degree directly from the phenotypes themselves, without needing detailed knowledge of the underlying genotype-phenotype map.

biophysics↗

bioRxiv2024

Creating a biomedical knowledge base by addressing GPT inaccurate responses and benchmarking context

We created GNQA, a generative pre-trained transformer (GPT) knowledge base driven by a performant retrieval augmented generation (RAG) with a focus on aging, dementia, Alzheimers and diabetes. We uploaded a corpus of three thousand peer reviewed publications on these topics into the RAG. To address concerns about inaccurate responses and GPT hallucinations, we implemented a context provenance tracking mechanism that enables researchers to validate responses against the original material and to get references to the original papers. To assess the effectiveness of contextual information we collected evaluations and feedback from both domain expert users and citizen scientists on the relevance of GPT responses. A key innovation of our study is automated evaluation by way of a RAG assessment system (RAGAS). RAGAS combines human expert assessment with AI-driven evaluation to measure the effectiveness of RAG systems. When evaluating the responses to their questions, human respondents give a "thumbs-up" 76% of the time. Meanwhile, RAGAS scores 90% on answer relevance on questions posed by experts. And when GPT-generates questions, RAGAS scores 74% on answer relevance. With RAGAS we created a benchmark that can be used to continuously assess the performance of our knowledge base. Full GNQA functionality is embedded in the free GeneNetwork.org web service, an open-source system containing over 25 years of experimental data on model organisms and human. The code developed for this study is published under a free and open-source software license at https://git.genenetwork.org/gn-ai/tree/README.md.

scientific communication and education↗

bioRxiv2023

Excitable Rho dynamics drive cell contractions by sequentially inducing ERM protein-mediated actin-membrane attachment and actomyosin contractility

Migration of endothelial and many other cells requires spatiotemporal regulation of protrusive and contractile cytoskeletal rearrangements that drive local cell shape changes. Unexpectedly, the small GTPase Rho, a crucial regulator of cell movement, has been reported to be active in both local cell protrusions and retractions, raising the question of how Rho activity can coordinate cell migration. Here we show that Rho activity is absent in local protrusions and active during retractions. During retractions, Rho rapidly activated ezrin-radixin-moesin proteins (ERMs) to increase actin-membrane attachment, and, with a delay, non-muscle myosin II (NMII). Rho activity was excitable, with NMII acting as a slow negative feedback regulator. Strikingly, inhibition of SLK/LOK kinases, through which Rho activates ERMs, caused elongated cell morphologies, impaired Rhoinduced cell contractions, and reverted Rho-induced blebbing. Together, our study demonstrates that Rho activity drives retractions by sequentially enhancing ERM-mediated actin-membrane attachment for force transmission and NMII-dependent contractility.

cell biology↗

bioRxiv2023

A Fluorogenic-Based Assay to Measure Chaperone-Mediated Autophagic Activity in Cells and Tissues

ObjectivePathologies including cardiovascular diseases, cancer, and neurological disorders are caused by the accumulation of misfolded / damaged proteins. Intracellular protein degradation mechanisms play a critical role in the clearance of these disease-causing proteins. Chaperone mediated autophagy (CMA) is a protein degradation pathway that employs chaperones to bind proteins, bearing a unique KFERQ-like motif, for delivery to a CMA-specific Lysosome Associated Membrane Protein 2a (LAMP2a) receptor for lysosomal degradation. To date, steady-state CMA function has been assessed by measuring LAMP2A protein expression. However, this does not provide information regarding CMA degradation activity. To fill this dearth of tools / assays to measure CMA activity, we generated a CMA-specific fluorogenic substrate assay. MethodsA KFERQ-AMC [Lys-Phe-Asp-Arg-Gln-AMC(7-amino-4-methylcou-marin)] fluorogenic CMA substrate was synthesized from Solid-Phase Peptide Synthesis. KFERQ-AMC, when cleaved via lysosomal hydrolysis, causes AMC to release and fluoresce (Excitation:355 nm, Emission:460 nm). Using an inhibitor of lysosomal proteases, i.e., E64D [L-trans-Epoxy-succinyl-leucylamido(4-guanidino)butane)], responsible for cleaving CMA substrates, the actual CMA activity was determined. Essentially, CMA activity = (substrate)fluorescence - (substrate+E64D) fluorescence. To confirm specificity of the KFERQ sequence for CMA, negative control peptides were used. ResultsHeart, liver, and kidney lysates containing intact lysosomes were obtained from 4-month-old adult male mice. First, lysates incubated with KFERQ-AMC displayed a time dependent (0-5 hour) increase in AMC fluorescence vs. lysates incubated with negative control peptides. These data validate the specificity of KFERQ for CMA. Of note, liver exhibited the highest CMA (6-fold; p<0.05) > kidney (2.4-fold) > heart (0.4-fold) at 5-hours. Second, E64D prevented KFERQ-AMC degradation, substantiating that KFERQ-AMC is degraded via lysosomes. Third, cleavage of KFERQ-AMC and resulting AMC fluorescence was inhibited in Human embryonic kidney (HEK) cells and H9c2 cardiac cells transfected with Lamp2a vs. control siRNA. Further, enhancing CMA using Lamp2a adenovirus upregulated KFERQ degradation. These data suggest that LAMP2A is required for KFERQ degradation. Conclusion. We have generated a novel assay for measuring CMA activity in cells and tissues in a variety of experimental contexts. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/571785v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@7d43d8org.highwire.dtl.DTLVardef@1f11b2eorg.highwire.dtl.DTLVardef@2fa165org.highwire.dtl.DTLVardef@10d276d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Proposed mechanism of KFERQ-AMC degradation via CMA C_FIG

biochemistry↗

bioRxiv2022

Simple Models For Neuroscience Research Discoveries: How Often Are These Models Used In Africa

Simple animal model systems such as Drosophila, Zebrafish, and C. Elegans have enabled numerous breakthroughs in understanding human health and disease. Their conserved biological processes, ever-expanding established procedures for handling, and amenability for molecular and genetic manipulation, in addition to the minimal ethical concerns, have made these models preferred choices in several life science disciplines globally. Owing to their cheap maintenance cost, adopting these model systems will help bridge the research gap between Africa and the Global North and contribute to advancing scientific knowledge in African universities through practical sessions. However, the extent to which these models are used across Africa is unknown. Here, we analysed the use of Drosophila, Zebrafish, and C. elegans model systems in scientific publications from African laboratories from the year 2000 to 2021. Of 1851 PubMed-indexed publications in which at least one simple animal model was mentioned, 168 used at least one of these models for the actual investigation. With an average of 21 articles per country, South Africa, Nigeria, Kenya, Egypt, Morocco, and Tunisia contributed 75% of these studies. The remaining 25% were contributed by seven other countries at 2-7 articles per country. From here, we extracted and analysed information on funding and international collaboration. This revealed that 24.4 % of the studies were exclusively funded locally, 28.57 % exclusively funded internationally, 15.5% received both local and international funding, and the rest (31.5%) were unfunded, revealing that there is satisfactory access to funds for simple animal model studies, especially from external funders. By analysing the pattern of collaborations, we show that most of these studies had international collaborations, while very few collaborated within Africa. Our work provides data on the current state of research using simple model systems in African laboratories and argues that incorporating these models will advance biomedical science research in Africa.

neuroscience↗

bioRxiv2022

Chlorpyrifos degradation by combined solar photo-Fenton and bacterial metabolism and simultaneous toxicity analysis in zebrafish (Danio rerio)

Chlorpyrifos (CP) is a widely used insecticide that has been used extensively, contributing towards a negative impact on public health concerns and associated ecosystems. Bioremediation is one of the key biological methods used for reducing these environmental toxicants. The present study examined the effectiveness of a combined process including solar photo-Fenton process followed by bacterial degradation using Ochrobactrum sp. CPD-03 for effective CP degradation in wastewater. Results showed that solar photo-Fenton treatment had CP degradation efficiency of ~42% in 4 h with a final degradation efficiency of ~92% in 96 h upon combined bacterial degradation. Simultaneous survivability of zebrafish (Danio rerio) was also studied during CP degradation. Compared to control, adult zebrafishes showed increased survivability following the addition of CPD-03 in water resulting a reduced CP concentration. CP toxicity in wastewater had caused acetylcholinesterase inhibition in zebrafish; however, this inhibition is due to absence of CP degrading bacteria. Therefore, a combined approach would influence for regulating CP degradation in wastewater along with simultaneous survival of Danio rerio.

microbiology↗