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Results for “cell biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2019

A novel nuclear speckle factor, USP42, promotes homologous recombination repair by resolving DNA double-strand break induced R-loop

The nucleus of mammalian cells is highly compartmentalized by nuclear bodies, including nuclear speckles. While nuclear bodies are known to function in regulating gene expression, their involvement in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, revealed that nuclear speckle factors regulating transcription are potentially involved in the regulation of HR. Among the top hits, we provide evidence showing that USP42, which is a deubiquitylating enzyme and a hitherto unidentified nuclear speckles factor, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection. We further showed that USP42 localizes to nuclear speckles via an intrinsically disordered region, which is required for efficient HR. Furthermore, we established that USP42 interacts with DHX9, which possesses DNA-RNA helicase activity, and is required for efficient resolution of DSB-induced R-loop. Mechanistically, USP42 antagonizes mono-ubiquitylation of DHX9 that is evoked after DSB induction. In conclusion, our data propose a model in which a novel nuclear speckle factor, USP42, facilitates DSB-induced R-loop resolution, BRCA1 loading to DSB sites and preferential DSB repair by HR, indicating the importance of spatial regulation of DSB repair choice mediated by nuclear bodies.\n\nSignificant statementDefects in the repair of DNA double-strand break (DSB), which is one of the most harmful DNA insults, cause human diseases including cancers. It has been suggested that DSBs generated in the coding region tend to be repaired by homologous recombination (HR) that is error-free DSB repair pathway. To reveal the spatial regulation of HR, in this study, we investigated the potential contribution of nuclear bodies, especially nuclear speckles, to HR, identifying a deubiquitylating enzyme USP42 as a HR promoting factor. We found that USP42 deubiquitylates DHX9, facilitates resolution of DNA-RNA hybrid structure and enhances HR through BRCA1 loading to DSB sites.\n\nClassificationBiological Sciences, Cell Biology

cell biology↗

bioRxiv2026

Generation, Characterization and Comparison of Ovine Induced Pluripotent and Embryonic-Disc Stem Cells

Pluripotent stem cells derived from livestock species represent valuable systems for studying early mammalian development and for establishing renewable, well-defined cell sources; however, direct comparative characterization of distinct pluripotent stem cell platforms in sheep remains limited. In this study, we established and evaluated two ovine pluripotent stem cell types: reprogrammed induced pluripotent stem cells (siPSCs) and embryonic disc-derived stem cells (sEDSCs). Both siPSCs and sEDSCs exhibited core features of pluripotency, including compact colony morphology, alkaline phosphatase activity, expression of key pluripotency-associated markers, and maintenance of a normal ovine karyotype. Flow cytometry and quantitative RT-PCR analyses revealed broadly overlapping yet distinguishable pluripotency marker expression profiles between the two cell types. Functional pluripotency was confirmed by embryoid body formation and in vitro differentiation into derivatives of all three germ layers. To further assess lineage-specific differentiation competence and compare functional outputs relevant to mesodermal differentiation, both pluripotent stem cell types were directed towards the adipogenic lineage. While siPSCs and sEDSCs were each capable of adipogenic differentiation, differences in differentiation efficiency and marker expression were observed. Together, these findings demonstrate that ovine siPSCs and sEDSCs share core pluripotency characteristics while retaining distinct molecular and functional properties, providing a robust comparative framework for studies of ovine pluripotency, lineage specification, and stem cell biology.

cell biology↗

bioRxiv2023

Genetic transformation of the frog-killing chytrid fungus Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis (Bd), a causative agent of chytridiomycosis, is decimating amphibian populations around the world. Bd belongs to the chytrid lineage, a group of early-diverging fungi that are widely used to study fungal evolution. Like all chytrids, Bd develops from a motile form into a sessile, growth form, a transition that involves drastic changes in its cytoskeletal architecture. Efforts to study Bd cell biology, development, and pathogenicity have been limited by the lack of genetic tools with which to test hypotheses about underlying molecular mechanisms. Here, we report the development of a transient genetic transformation system for Bd. We used electroporation to deliver exogenous DNA into Bd cells and detected transgene expression for up to three generations under both heterologous and native promoters. We also adapted the transformation protocol for selection using an antibiotic resistance marker. Finally, we used this system to express fluorescent protein fusions and, as a proof of concept, expressed a genetically encoded probe for the actin cytoskeleton. Using live-cell imaging, we visualized the distribution and dynamics of polymerized actin at each stage of the Bd life cycle, as well as during key developmental transitions. This transformation system allows, for the first time, direct testing of key hypotheses regarding mechanisms of Bd pathogenesis. This technology also paves the way for answering fundamental questions of chytrid cell, developmental, and evolutionary biology.

cell biology↗

bioRxiv2025

Inferring single-cell dynamics of a molecular reporter from unlabeled live-cell light microscopy data analyzed with delay embedding

Quantification of the temporal sequence of molecular behavior in live individual cells holds promise for improving causal and mechanistic models of cell biology. In recent years, different methods for inferring molecular labeling from microscopy data have been developed, especially in the context of "virtual pathology", but less effort has been directed to the context of single-cell dynamics and live-cell imaging. We demonstrate that phase-contrast live-cell imaging of MCF10A cells, without labeling data, is predictive of dynamical, single-cell behavior of the cell-cycle reporter Human DNA Helicase B (HDHB) - in particular, of the nuclear vs. cytoplasmic localization of this fluorescent reporter of cyclin-dependent kinase activity. Prediction quality improves substantially when temporal sequences of images are combined in a "delay embedding" framework. When different featurizations of the imaging data are examined, we find that features derived from a variational auto-encoder (VAE) outperform "classical" image features derived from shape and texture. We find the best performance, with Pearson R[~] 0.9 on test data, using VAE features augmented by categorical predictions, all within the delay-embedding framework - in comparison to R [~] 0.5 based on "ordinary" regression with VAE features.

cell biology↗

bioRxiv2025

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Midbody Remnant Proteins Following Epithelial-Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenic process that allows highly polarized, immotile epithelial cells to transform into motile mesenchymal cells: it is a fundamental cellular process involved in embryonic development, tumour cell metastasis, organ fibrosis and tissue regeneration. To assess the contribution of secreted midbody remnants (MBRs) - a new class of membranous extracellular vesicle (EV) molecularly distinct from exosomes/small EVs - to the EMT process, we conducted a proteomic analysis of MBRs released from Madin-Darby canine kidney (MDCK) cells, and MDCK cells transformed with oncogenic H-Ras (21D1 cells). MBRs were harvested from cell culture media in milligram quantities using a continuous culture bioreactor device and purified using sequential centrifugation and buoyant density gradient centrifugation (OptiPrep). Gel-MS/MS protein profiling showed MDCK cell-MBRs reflect their epithelial origin (e.g., enriched CDH1, DSP, THBS1, OLCN, EPCAM proteins) and 21D1 cell-MBRs their mesenchymal phenotype (e.g., HRAS, VIM, MMP14, CDH2, WNT5A and enriched invasive and cell motility proteins). Prominent findings were the unique expression of the immune checkpoint protein NT5E/CD73 (ecto-5'-nucleotidase), and ser/thr kinases LIMK1/K2 in 21D1-MBRs (not present in MDCK cell-MBRs), and enrichment in Wnt signalling network proteins. Collectively, our findings suggest MBRs might play a previously unrecognized role in the EMT process. SignificanceO_LIEpithelial-to-mesenchymal transition (EMT) is a critical cell biological process that occurs during normal embryonic development and cancer progression. Our study describes, for the first time, the large-scale sequential purification of secreted midbody remnants (MBRs) and exosomes/sEVs from the in vitro cell line EMT model Madin-Darby canine kidney (MDCK) cells and MDCK cells transformed with oncogenic H-Ras (21D1 cells): GeLC-MS/MS protein profiling identified the repertoire of enriched MDCK-MBR proteins following EMT. C_LIO_LIMBRs display a proteome profile distinct from sEVs that is enriched with factors of the centralspindlin complex (KIF23.1, KIF4A, INCENP, CEP55, PLK1) and further include components of the mitochondrial network, cytokinesis, microtubule movement, and intercellular connection. C_LIO_LIIn the context of EMT, our data reveal simultaneous activation of EMT signalling pathways in MBRs including signalling receptor binding, regulation of cell differentiation, and Wnt, VEGF and PDGF signalling. C_LIO_LIWe identify several mesenchymal enriched networks in MBRs associated with focal adhesion, cell matrix, kinase activity, and cell shape/organisation, while epithelial derived MBRs are show enriched networks predominately associated with mitochondrial (processing/transport), midbody, and plasma membrane annotation. C_LIO_LIOur study sheds light on the signalling architecture of MBRs following oncogenic H- Ras-induced EMT: collectively, our data informs ongoing efforts to delineate oncogenic drivers of cancer initiation, progression, and metastasis. C_LI

cell biology↗

bioRxiv2025

Loss of ciliary proteins IFT20 and IFT88 results in defective phagocytosis and metabolism in the RPE

A major proportion of retinal disease-causing genes are related to the primary cilium, a microtubule-based signalling organelle essential for multiple developmental pathways. Previous work has shown that the primary cilium plays a crucial role in the development of the retinal pigment epithelium (RPE) affecting homeostasis and function, in particular phagocytosis. We used a cell biology approach to analyse the influence of ciliary genes on RPE phagocytosis and dissect the underlying molecular mechanisms. We found that loss of ciliary trafficking via depletion of Ift20 and Ift88 in RPE-J cells resulted in impaired phagocytosis, specifically by reducing photoreceptor outer segments binding, changes in apical membrane morphology and altered mitochondrial metabolism, whereas loss of Bbs6 showed no functionality phenotype. In addition, proteomics revealed mis-regulated pathways and targets, through which new phagocytosis-related proteins were identified. Our data highlight the role of primary cilia proteins in RPE function and metabolism, essential for visual health.

cell biology↗

bioRxiv2025

ORP5 controls the partitioning of phosphatidic acid between triacylglycerol and cardiolipin synthesis at mitochondria-ER-lipid droplet contact sites

Phosphatidic acid (PA) is a central metabolic intermediate that can fuel triacylglycerol (TAG) synthesis in lipid droplets (LDs) or cardiolipin production in mitochondria, but how cells partition PA between these competing fates has remained a fundamental unresolved question in lipid cell biology. We identify the lipid transfer protein ORP5 as a key regulator of PA partitioning at Mitochondria-Associated endoplasmic reticulum Membranes (MAM) that contact lipid droplets (LD), referred to as MAM-LD junctions. Cell imaging analysis shows that ORP5 stabilizes PA levels at MAM to promote TAG synthesis. On the other hand, loss of ORP5 causes PA accumulation on mitochondrial membranes, leading to excess cardiolipin synthesis and mitochondrial hyperfusion, while impairing triacylglycerol (TAG) synthesis and LD formation. Finally, reconstitution assays using liposomes or giant organelles further demonstrate that ORP5 can transfer PA from mitochondria to the ER via its ORD domain. Together, these findings reveal that ORP5 functions as a PA lipid transfer protein at tripartite MAM-LD contacts, where it balances LD formation with mitochondrial lipid metabolism, protecting mitochondria from cardiolipin overload.

cell biology↗

bioRxiv2021

Courtship ritual of male and female nuclei during fertilisation in Neurospora crassa

Sexual reproduction is a key process influencing the evolution and adaptation of animals, plants and many eukaryotic microorganisms, such as fungi. Mycologists have described the different fungal fruiting bodies, while geneticists have partly unravelled the regulation of sexual development. However, the sequential fungal cell biology of fertilisation and the associated nuclear dynamics after plasmogamy are poorly understood. Using histone-fluorescent parental isolates, we tracked male and female nuclei during fertilisation in the model ascomycetes Neurospora crassa using live-cell-imaging. This study unravels the behaviour of trichogyne resident female nuclei and the extraordinary manner that male nuclei migrate up the trichogyne to the protoperithecium. Our observations raise new fundamental questions about the modus operandi of nuclei movements during sexual reproduction, male and female nuclear identity, guidance of nuclei within the trichogyne and, unexpectedly, the avoidance of "polyspermy" in fungi. The spatio-temporal dynamics of male nuclei within the trichogyne following plasmogamy are also described, where the speed and the deformation of male nuclei are of the most dramatic observed to date in a living organism.

cell biology↗

bioRxiv2024

A Novel Cell Culture Scratch Assay Platform Generates Reproducible Gaps for Quantitative Cell Movement-Based Studies

Scratch assays are routinely performed for multiple research applications in cell biology (i.e., migration, metastasis, repair mechanisms, etc.). Conventional scratches are usually generated with pipette tips. User inconsistencies and varying pipette tips are major obstacles to reproducibility and quantitative power. Here, we present a novel, scratch/gap generating, cell culture plate-based, platform that addresses these issues, providing consistency and reproducibility across multiple users, significantly reducing variability, and increasing quantitative outcomes.

cell biology↗

bioRxiv2024

Phospholipase D3 regulates TFEB/TFE3 metabolism to maintain lysosomal homeostasis

Phospholipase D3 (PLD3) is a lysosomal protein in neurons and is linked to an Alzheimers disease (AD) risk through coding variants. Its role in lysosomal abnormalities observed in AD remains unclear. We conducted a comprehensive study integrating transcriptomic, proteomic, and cell biology approaches to investigate PLD3s role in lysosome function in neurons. PLD3 undergoes aberrant ubiquitination in AD brain tissue, leading to altered protein abundance and subcellular location. We assessed the lysosomal proteome in SH-SY5Y cells with PLD3 knockout and found PLD3-/- cells had higher levels of proteins related to lysosomal biogenesis, endocytosis, and calcium signaling. Loss of PLD3 caused an enlargement in neuronal lysosome size, increased endocytic activity and a decline in lysosomal clearance of aggregated human {beta}-amyloid or -synuclein, despite increased expression level and activity of cathepsin B. PLD3-deficiency increase the level and transcriptional activity of transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3), suggesting a role for PLD3 in regulating lysosomal biogenesis. In summary, we found that PLD3 is required to maintain neuronal lysosomal function.

cell biology↗

bioRxiv2025

Subcellular proteomics of Paradiplonema papillatum reveals digestive capacity of the cell membrane and the plasticity of peroxisomes across euglenozoans

Diplonemids are among the most diverse and abundant protists in the deep ocean, have extremely complex and ancient cellular systems, and exhibit unique metabolic capacities. Despite this, we know very little about this major group of eukaryotes. To establish a model organism for comprehensive investigation, we performed subcellular proteomics on Paradiplonema papillatum and localized 4,870 proteins to 22 cellular compartments. We additionally confirmed the predicted location of several proteins by epitope tagging and fluorescence microscopy. To probe the metabolic capacities of P. papillatum, we explored the proteins predicted to the cell membrane compartment in our subcellular proteomics dataset. Our data revealed an accumulation of many carbohydrate active enzymes (CAZymes). Our predictions suggest that these CAZymes are exposed to extracellular space, supporting proposals that diplonemids may specialize in breaking down carbohydrates in plant and algal cell walls. Further exploration of carbohydrate metabolism revealed an evolutionary divergence in the function of glycosomes (modified peroxisomes) in diplonemids versus kinetoplastids. Our subcellular proteome provides a resource for future investigations into the unique cell biology of diplonemids.

cell biology↗

bioRxiv2025

BMP and NODAL Paracrine Signalling Regulate the Totipotent-like Cell State in Embryonic Stem Cells.

1)Cell-cell communication coordinates signalling between cells to guide context-dependent cell fate decisions such as proliferation, differentiation, and lineage specification. Such communication mechanisms are poorly understood in regulating the stem cell states. In this study, we investigate how cell-cell communication regulates cell fate transitions in heterogeneous embryonic stem cell populations, with a particular focus on totipotent-like cells that resemble the two-cell stage embryo. Using single-cell RNA sequencing in combination with computational frameworks, we map ligand- receptor interactions and model downstream regulatory effects across various stem cell states. We functionally validate the predictions by selectively perturbing signalling pathways under specific culture conditions. Our data reveal the key roles of BMP and NODAL (TGF-{beta}) signalling in mediating intercellular communication to shape stem cell identity and heterogeneity. These findings enhance our understanding of the signalling logic that governs early developmental cell fate decisions, providing new insights into stem cell biology with broad implications for regenerative medicine and developmental modelling.

cell biology↗

bioRxiv2019

Robust organelle size control via bursty growth

One of the grand challenges in quantitative cell biology is understanding the precision with which cells assemble and maintain subcellular organelles. A critical property that governs organelle function is its size. Organelle sizes must be flexible enough to allow cells to grow or shrink them as environments demand, yet be maintained within homeostatic limits. Despite identification of numerous molecular factors that regulate organelle sizes we lack insight into the quantitative principles underlying organelle size control. Here we examine organelle sizes from Saccharomyces cerevisiae and human iPS cells with mathematical theory to show that cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship we predict theoretically, our framework suggests that organelles grow in random bursts from a limited pool of building blocks. Burst-like growth provides a general biophysical mechanism by which cells can maintain on average reliable yet plastic organelle sizes.

systems biology↗

bioRxiv2021

IntAct: a non-disruptive internal tagging strategy to study actin isoform organization and function

Actin plays a central role in many cell biological processes including division and motility. Mammals have six, highly conserved actin isoforms with nonredundant biological functions, yet the molecular basis of isoform specificity remains elusive due to a lack of tools. Here, we describe the development of IntAct, an internal tagging strategy to study actin isoform function in fixed and living cells. We first identified a residue pair in {beta}-actin that permits non-disruptive tag integration. Next, we used knock-in cell lines to demonstrate that the expression and filament incorporation of IntAct {beta}-actin is indistinguishable from wildtype. Furthermore, IntAct {beta}-actin remains associated with actin-binding proteins profilin, cofilin and formin family members DIAPH1 and FMNL2 and can be targeted in living cells. To demonstrate the usability of IntAct for actin isoform investigations, we also generated IntAct {gamma}-actin cells and show that actin isoform specific distribution remains unaltered in human cells. Moreover, introduction of tagged actin variants in yeast demonstrated an expected variant-dependent incorporation into patches and filaments. Together, our data indicate that IntAct is a versatile tool to study actin isoform localization, dynamics and molecular interactions.

cell biology↗

bioRxiv2021

Cell tip growth underlies injury response of marine macroalgae

Regeneration is a widely observed phenomenon by which the integrity of an organism is recovered after damage. So far, studies on the molecular and cellular mechanisms of regeneration have been limited to a handful of model multicellular organisms. Here, we systematically surveyed the regeneration ability of marine macroalgae (Rhodophyta, Phaeophyceae, Chlorophyta) after thallus severing and applied live cell microscopy on them to uncover the cellular response to the damage. We observed three types of responses - budding, rhizoid formation and/or sporulation - in 25 species among 66 examined, demonstrating the high potential of regeneration of macroalgae. In contrast, callus formation, which often accompanies plant regeneration, was never observed. We monitored the cellular and nuclear dynamics during cell repair or rhizoid formation of four phylogenetically diverged Rhodophyta and Chlorophyta species (Colaconema sp., Dasya sessilis, Cladophora albida, Codium fragile). We observed tip growth of the cells near the damaged site as a common response, despite the difference in the number of nuclei and cells across species. Nuclear translocation follows tip growth, enabling overall uniform distribution of multinuclei (Dasya sessilis, Cladophora albida, Codium fragile) or central positioning of the mononucleus (Colaconema sp.). In contrast, the control of cell cycle events, such as nuclear division and septation, varied in these species. In Dasya sessilis, the division of multinuclei was synchronised, whereas it was not the case in Cladophora albida. Septation was tightly coupled with nuclear division in Colaconema and Dasya but not in others. These observations show that marine macroalgae utilise a variety of regeneration pathways, with some common features. This study also provides a novel methodology of live cell biology in macroalgae, offering a foundation for the future of this under-studied taxon.

cell biology↗

bioRxiv2024

Inheritance of old mitochondria controls early CD8+ T cell fate commitment and is regulated by autophagy

T cell immunity is impaired during ageing, particularly in memory responses needed for efficient vaccination. Autophagy and asymmetric cell division (ACD) are cell biological mechanisms key to memory formation, which undergo a decline upon ageing. However, despite the fundamental importance of these processes in cellular function, the link between ACD and in vivo fate decisions has remained highly correlative in T cells and in the field of mammalian ACD overall. Here we provide robust causal evidence linking ACD to in vivo T cell fate decisions and our data are consistent with the concept that initiation of asymmetric T cell fates is regulated by autophagy. Analysing the proteome of first-daughter CD8+ T cells following TCR-triggered activation, we reveal that mitochondrial proteins rely on autophagy for their asymmetric inheritance and that damaged mitochondria are polarized upon first division. These results led us to evaluate whether mitochondria were asymmetrically inherited and to functionally address their impact on T cell fate. For this we used a novel mouse model that allows sequential tagging of mitochondria in mother and daughter cells, enabling their isolation and subsequent in vivo analysis of CD8+ T cell progenies based on pre-mitotic cell cargo. Autophagy-deficient CD8+ T cells showed impaired clearance and symmetric inheritance of old mitochondria, suggesting that degradation events promote asymmetry and are needed to generate T cells devoid of old organelles. Daughter cells inheriting old mitochondria are more glycolytic and upon adoptive transfer show reduced memory potential, whereas daughter cells that have not inherited old mitochondria from the mother cell are long-lived and expand upon cognate-antigen challenge. Proteomic and single-cell transcriptomic analysis of cells inheriting aged mitochondria suggest that their early fate divergence relies on one carbon metabolism as a consequence of poor mitochondrial quality and function. These findings increase our understanding of how T cell diversity is early-imprinted during division and will help foster the development of strategies to modulate T cell function. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/577412v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@526135org.highwire.dtl.DTLVardef@6c04b1org.highwire.dtl.DTLVardef@1a834fforg.highwire.dtl.DTLVardef@2f70f8_HPS_FORMAT_FIGEXP M_FIG The MitoSnap model allows tracking of pre-mitotic and post-mitotic cell cargoes. Both segregation and degradation (autophagy) contribute to the asymmetric inheritance of old mitochondria. Old mitochondria impact cell metabolism and function. Cells devoid of old mitochondria exhibit better memory potential in vivo. C_FIG

cell biology↗

bioRxiv2025

Addressing complex autofluorescence signatures in solid tissue samples to enhance full spectrum flow cytometry of non-immune cells.

FSFC is an emerging technology that can greatly enhance our understanding of the single-cell proteomic landscape. However, its application to cells derived from solid tissues has been hampered by their complex autofluorescence signatures and lack of optimized tools for non-immune cells. Here, we present a protocol and discuss key controls that minimize the impact of unmixing errors enabling us to resolve multiple EC subpopulations isolated from different tissues in models of chronic tissue injury. Research Topic(s)Vascular biology, cell heterogeneity, full spectrum flow cytometry Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/695385v2_ufig1.gif" ALT="Figure 1000"> View larger version (43K): org.highwire.dtl.DTLVardef@1745181org.highwire.dtl.DTLVardef@1930db9org.highwire.dtl.DTLVardef@16a0b3dorg.highwire.dtl.DTLVardef@107ec29_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsOptimisation of a FSFC panel to enable in-depth phenotyping of tissue- and model-specific endothelial subpopulations from solid tissues. Discussion of appropriate controls to minimize the impact of tissue autofluorescence and enhance the signal-to-noise ratio for cell phenotyping in complex models of inflammation and fibrosis. Trajectory analysis to track cellular plasticity over time. Application of full spectrum cell sorting to isolate rare endothelial subpopulations with complex phenotypes.

cell biology↗

bioRxiv2026

Integration of single-cell multi-omic data with graph-based topic modelling

Recent advances in single-cell biology enable the profiling of multiple molecular layers, such as the transcriptome, epigenome, and surface proteins, within a single cell. Tackling the complexity of these data from different perspectives allows researchers to get the most complete insights into the biological properties of cells. Here, we propose a graph-based topic modelling method called bionSBM. Our method leverages well-known community-detection methods for multipartite graphs and the interpretability of topic modelling to cluster and explain high-dimensional, sparse, and noisy single-cell matrices. We applied our algorithm to paired single-cell multi-omics data, such as 10X Multiome, SHARE-seq, and CITE-seq. We showed that it achieves superior performance compared to state-of-the-art methods for ground-truth label retrieval, with high specificity and distinct biological interpretability.

bioinformatics↗