Biology subjects

Singh, S.

Publications and source records attributed to Singh, S..

At least 199 records · Page 11Linked to original sources

bioRxiv2024

Faster amylin aggregation on fibrillar collagen hastens diabetic progression through β cell death and loss of function

Amyloid deposition of the neuroendocrine peptide amylin in islet tissues is a hallmark of type 2 diabetes (T2DM), leading to {beta}-cell toxicity through nutrient deprivation, membrane rupture and apoptosis. Though accumulation of toxic amylin aggregates in islet matrices is well documented, the role of the islet extracellular matrix in mediating amylin aggregation and its pathological consequences remains elusive. Here, we address this question by probing amylin interaction with collagen I (Col I)--whose expression in the islet tissue increases during diabetes progression. By combining multiple biophysical techniques, we show that hydrophobic, hydrophilic & cation-{pi} interactions regulate amylin binding to Col I, with fibrillar collagen driving faster amylin aggregation. Amylin-entangled Col I matrices containing high amounts of amylin induce death and loss of function of INS1E {beta}-cells. Together, our results illustrate how amylin incorporation in islet matrices through amylin-Col interactions drives T2DM progression by impacting {beta}-cell viability and insulin secretion.

biophysics↗

bioRxiv2024

Adversarial learning enables unbiased organism-wide cross-species alignment of single-cell RNA data

Todays single-cell RNA (scRNA) datasets remain siloed, due to significant challenges associated with their integration at scale. Moreover, most scRNA analysis tools that operate at scale leverage supervised techniques that are insufficient for cell-type identification and discovery. Here, we demonstrate that the alignment of scRNA data using unsupervised models is accurate at an organism-wide scale and between species. To do this, we show adversarial training of a deep-learning model we term batch-adversarial single-cell variational inference (BA-scVI) can be employed to align standardized benchmark datasets comprising dozens of scRNA studies spanning tissues in humans and mice. In the aligned space, we analyze cell types that span tissues in both species and find prevalent complement expressing macrophages and fibroblasts. We provide access to the tools presented via an online interface for atlas exploration and reference-based drag-and-drop alignment of new data.

genetics↗

bioRxiv2024

Transcriptomic Meta-analysis Identifies Long Non-Coding RNAs Mediating Zika's Oncolytic Impact in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is an aggressive and lethal form of brain cancer with few effective treatments. In this context, Zika virus has emerged as a promising therapeutic agent due to its ability to selectively infect and kill GBM cells. To elucidate these mechanisms and expand the landscape of oncolytic virotherapy, we pursued a transcriptomic meta-analysis comparing the molecular signatures of Zika infection in GBM and neuroblastoma (NBM). Over-representation analysis of dysregulated coding genes showed significant enrichment of tumor necrosis factor (TNF), NF-{kappa}B, and p53 signaling pathways. A refined list of long non-coding RNAs consistently dysregulated in Zika-infected GBMs was also developed. Functional review of these candidates revealed their potential regulatory role in Zika-mediated oncolysis. We performed validation of the less-researched targets in adult and pediatric GBM cell lines and found significant differential regulation, as predicted. Altogether, our results provide novel insights into the molecular mechanisms underlying the effect of Zika on GBM. We highlight potential therapeutic targets that could be further interrogated to improve the efficacy of tumor cell death and the utility of Zika as an adjuvant virotherapy for GBM and other related cancers.

cancer biology↗

bioRxiv2024

Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC). Mechanistically, cyclin A/Bi hyperactivate E2F1 and cyclin B by blocking their RxL-interactions with cyclin A and Myt1, respectively, ultimately leading to SAC activation and mitotic cell death. Base editor screens identified cyclin B variants that confer cyclin A/Bi resistance including several variants that disrupted cyclin B:Cdk interactions. Unexpectedly but consistent with our base editor and knockout screens, cyclin A/Bi induced the formation of neo-morphic Cdk2-cyclin B complexes that promote SAC activation and apoptosis. Finally, orally-bioavailable cyclin A/Bi robustly inhibited tumor growth in chemotherapy-resistant patient-derived xenograft models of SCLC. This work uncovers gain-of-function mechanisms by which cyclin A/Bi induce apoptosis in cancers with high E2F activity, and suggests cyclin A/Bi as a therapeutic strategy for SCLC and other cancers driven by high E2F activity.

cancer biology↗

bioRxiv2024

Horizontal transfer of nuclear DNA in transmissible cancer

Although somatic cell genomes are usually entirely clonally inherited, nuclear DNA exchange between cells of an organism can occur sporadically by cell fusion, phagocytosis or other mechanisms1-3. This phenomenon has long been noted in the context of cancer, where it could be envisaged that DNA horizontal transfer plays a functional role in disease evolution4-13. However, an understanding of the frequency and significance of this process in naturally occurring tumours is lacking. The host-tumour genetic discordance of transmissible cancers, malignant clones which pass between animals as allogeneic grafts, provides an opportunity to investigate this. We screened for host-to-tumour horizontal transfer of nuclear DNA in 174 tumours from three transmissible cancers affecting dogs and Tasmanian devils, and detected a single instance in the canine transmissible venereal tumour (CTVT). This involved introduction of a 15-megabase dicentric genetic element, composed of 11 rearranged fragments of six chromosomes, to a CTVT sublineage occurring in Asia around 2,000 years ago. The element forms the short arm of a small submetacentric chromosome, and derives from a dog with ancestry associated with the ancient Middle East. The introduced DNA fragment is transcriptionally active and has adopted the expression profile of CTVT. Its 143 genes do not, however, confer any obvious advantage to its spatially restricted CTVT sublineage. Our findings indicate that nuclear DNA horizontal transfer, although likely a rare event in tumour evolution, provides a viable mechanism for the acquisition of genetic material in naturally occurring cancer genomes.

cancer biology↗

bioRxiv2024

Logical Network Perturbations Guide Precise Target Prioritization for Drug Development

Despite advances in artificial intelligence (AI), target-based drug development remains costly, complex, and imprecise. We introduce F.O.R.W.A.R.D [Framework for Outcome-based Research and Drug Development], a network-based target prioritization platform, and demonstrate its utility in the challenging landscape of Inflammatory Bowel Diseases (IBD), a chronic, multifactorial condition. F.O.R.W.A.R.D uses real-world clinical outcomes, and a machine-learning classifier trained on transcriptomic data from seven prospective randomized trials across four drugs. It defines remission at the molecular level and calculates, using network connectivity, the likelihood that targeting a given molecule will induce remission-associated gene expression. Benchmarking against 210 completed trials across 52 targets, F.O.R.W.A.R.D achieved 100% predictive accuracy--despite variability in drug mechanisms and trial designs. Single-cell RNA-seq and a prospective biobank of patient-derived organoids confirmed that the remission signature is epithelium-specific and tracks with poor outcomes. F.O.R.W.A.R.D enables in-silico phase zero trials to inform trial design, revive shelved drugs, and guide early termination decisions. Broadly applicable and iteratively refined by emerging trial data, F.O.R.W.A.R.D has the potential to reshape drug discovery--bringing foresight to hindsight, and empowering both R&D and human-in-the-loop clinical decision-making.

bioinformatics↗

bioRxiv2024

Discordance in Genotypic and Phenotypic anti-tuberculosis drug susceptibility results: time to reconsider critical concentration.

ObjectiveTo correlate rpoB mutations found on the sanger sequencing in Mycobacterium tuberculosis (MTB) isolates with Minimum Inhibitory Concentrations (MICs) to the rifampicin. MethodsWe assessed the minimum inhibitory concentrations (MICs) for 151 archived clinical MTB isolates that were determined phenotypically susceptible to RIF (101;66.89%) and remaining fifty (50;33.11%) were resistant to RIF by BACTEC MGIT SIRE DST. MIC values were determined using colorimetric redox indicator (Resazurin/REMA) method and results were correlated with rpoB gene mutations associate with rifampicin resistance found. ResultsComparing the MIC and critical concentration, we found that 15 of these 101 (14.85%) isolates were misclassified by MGIT-960 as sensitive at standard critical concentration (1.0{micro}g/mL) though these were found to have low-level RIF resistance by CRI assay (MIC 0.50{micro}g/mL to 1.0{micro}g/mL) and sanger sequencing. We found that all of 15 isolates contained non-synonymous mutations, the commonest being the Ile572Phe (7, 46.66%), followed by Leu533Pro (3, 20.0%), His526Leu (2, 13.33%), His526Asn+Ile572Phe (1), Asp516Tyr (1), and Leu533Pro+Pro564Arg (1). These mutations are reported to confer low-level RIF resistance. But we did not find any mutation at MIC <0.25g/mL. ConclusionWe found that a significant number of MTB isolates have phenotypic and genotypic discordance. Taking 1.0{micro}g/mL of rifampicin as critical concentration, isolates from approximately 15% patients are misidentified as susceptible to rifampicin, even when these strains carry low level drug resistance conferring mutations and have potential to develop clinical MDR-TB.

microbiology↗

bioRxiv2024

Step Forward Cross Validation for Bioactivity Prediction: Out of Distribution Validation in Drug Discovery

Recent advances in machine learning methods for materials science have significantly enhanced accurate predictions of the properties of novel materials. Here, we explore whether these advances can be adapted to drug discovery by addressing the problem of prospective validation - the assessment of the performance of a method on out-of-distribution data. First, we tested whether k-fold n-step forward cross-validation could improve the accuracy of out-of-distribution small molecule bioactivity predictions. We found that it is more helpful than conventional random split cross-validation in describing the accuracy of a model in real-world drug discovery settings. We also analyzed discovery yield and novelty error, finding that these two metrics provide an understanding of the applicability domain of models and an assessment of their ability to predict molecules with desirable bioactivity compared to other small molecules. Based on these results, we recommend incorporating a k-fold n-step forward cross-validation and these metrics when building state-of-the-art models for bioactivity prediction in drug discovery.

bioinformatics↗

bioRxiv2024

TGFb-ANGPT2-Tie2 axis in cancer-associated fibroblasts reprograms oral cancer cells to embryonic-like cell state with predictive significance of poor prognosis

Myofibroblastic cancer-associated fibroblasts (CAFs) in tumor stroma is identified as poor-prognostic indicator in oral cancer; however, biological mechanisms are largely unexplored. Here, we discovered the role of autocrine or exogenous transforming growth factor beta (TGF{beta}) in inducing Tunica Interna Endothelial cell kinase 2 (Tie2) -signaling through histone deacetylase-mediated downregulation of Tie2-antagonist, Angiopoietin-2 in CAFs, responsible for induction and maintenance of myofibroblastic differentiation. To understand the influence of CAF-specific Tie2-signaling on cancer cell properties, we performed CAF-Cancer cell co-culture and its single-cell RNA sequencing (scRNA-Seq). Distinct clustering of CAFs suggested their transcriptional heterogeneity, driven by TGF{beta}-Tie2 activation. Interestingly, CAF-specific Tie2-signaling was responsible to reprogram cancer cells, producing embryonic-like cell state with increased stemness and EMT signatures. Importantly, both the Tie2-specific gene expression signature as well as reprogrammed cancer cell specific gene expression modules were validated respectively in fibroblasts clusters and malignant cell clusters in two independent earlier reported scRNAseq studies of HNSCC tumors. Highlighting the translatability of our study, the gene expression signature derived from reprogrammed cancer cells showed significant association with poor prognosis in HNSCC patient of TCGA cohort. Pharmacological inhibition of Tie2-signaling in CAFs, significantly abrogated the tumor initiating ability of co-cultured oral cancer cell lines. Overall, combining our molecular and computational analysis, we may propose Tie2 as a novel factor responsible for CAF mediated cancer cell plasticity, associated with aggressive nature of oral cancer. TeaserTie2-signaling is activated in myofibroblasts which impacts the behaviour of malignant cells by inducing cancer cell plasticity to acquire stemness.

cancer biology↗

bioRxiv2024

Autoimmunity and clinical pathology amelioration in SLE by Dexamethasone primed Mesenchymal Stem Cell derived conditioned media

This study proposes a novel approach, utilizing cell-free dexamethasone (Dex) primed Whartons jelly mesenchymal stem cells derived conditioned media (DW), offering improved efficacy, simplicity, and alternative medicine for addressing complications associated with systemic lupus erythematosus (SLE). This study explores the immunomodulatory effects of DW treatment on immune cell populations in SLE patients and a pristane-induced lupus (PIL) mouse model. DW induces significant expansion of Tregs, Bregs, suppressing Th17, double-negative T cells, and inflammatory neutrophils through modulating IL-10 and IL-17A production. Comparisons with the standard drug hydroxychloroquine reveal similar effects, suggesting TGF beta; pathway mediation in DWs actions. Compared with the immunosuppressive drug Dex, DW better attenuated autoantibody production, increased anti-inflammatory cytokines and maintained a balanced Th17/Treg ratio. In the preclinical in vivo studies, DW exhibits therapeutic efficacy, reducing mortality, preventing proteinuria, and reversing limb inflammation, seizure and alopecia. Organ specific evaluations using advanced live imaging or histopathological analysis highlighted DWs protective effects on kidneys, liver, lungs, heart, and spleen. This provided insight into the immunomodulatory benefits of DW at various levels and suggested that it could be a potential therapeutic avenue for managing complications related to SLE.

immunology↗

bioRxiv2024

Calibrated prediction of scarce adverse drug reaction labels with conditional neural processes

Adverse drug reactions (ADRs) are a major source of concern in the development of novel pharmaceuticals. ADRs may be identified in the late stages of development or even after commercialization, which may lead to failure or discontinuation after spending enormous resources on candidate molecules. Thus, predicting ADRs early in the process could help reduce costs by avoiding future failures. However, due to the low number of drugs approved, the amount of historical datapoints on ADRs is limited, which makes their prediction challenging for traditional chemoinformatics methods. Interestingly, each approved drug may have been annotated for hundreds of ADRs, which opens the door to framing ADR prediction as a multi-task or meta-learning problem. In this work, we adopt a meta-learning approach to ADR prediction by applying conditional neural processes (CNPs) to the publicly available Side Effect Resource (SIDER). Our results suggest that CNPs are competitive against single-task baselines even when trained on sparse datasets with missing labels. Furthermore, we find that their predictions are well-calibrated. Finally, we evaluate their performance on ADRs associated to different physiological systems and confirm good predictions across organ classes. Our findings suggest that meta-learning strategies may be beneficial for data-limited clinical endpoints like ADRs.

bioinformatics↗

bioRxiv2024

Cell morphological representations of genes enhance prediction of drug targets

Identifying a chemicals mechanism of action on biological systems is critical for drug development. A compounds mechanism can sometimes be identified by matching its image-based morphological profile to a well-annotated library. We enhance this approach by incorporating gene representations, demonstrating improved classification performance compared to direct matching methods. These representations are generated using morphological profiles of cells with artificially altered gene expression. A transformer model is trained to classify gene-compound pairs as true or false interactions, using both gene and compound profiles. The model then ranks likely target genes for unseen compounds. The strategy performs well for compounds targeting known genes but has limited effectiveness for novel targets, likely due to the current dataset size. However, the performance increase over existing profile-matching methods is notable. Future work with expanded datasets may enhance predictive capabilities, potentially accelerating early-stage drug discovery by improving target identification for novel compounds.

bioinformatics↗

bioRxiv2024

A first-in-Plasmodium study on tRNA intron splicing endonuclease PfTSEN1 and its substrate expression in clinical stage malaria

Mature tRNAs play critical role in several cellular processes including protein translation, post-translational-modifications and programmed-cell-death. Maturation of pre-tRNAs require removal of 5-leaders, 3-trailers, splicing of introns and addition of conserved 3-terminal CCA sequence. The tRNA splicing mechanism, an essential step in tRNA maturation govern by a tRNA splicing endonuclease. While the existence of functional tRNA splicing endonuclease(s) in Plasmodium falciparum has not been identified, its significance in other eukaryotes suggests a potential role in tRNA splicing event. Our study identified total tRNAs in Plasmodium and characterize a PftRNA splicing endonuclease (annotated as PfTSEN1) recognised recently as a component of ribonucleoprotein (RNP) complex, and synthesized a naphthoquinone derivative as a novel anti-malarial compound ( TSENi) targeting the functional activity of this protein. Enzyme activity assays elucidated that PfTSEN1 catalyses splicing of in vitro transcribed pre-tRNAleu, the expression of which was confirmed during the clinical stages of malaria parasite by RT-PCR. Interestingly, TSENi binds to and inhibits enzymatic activity of PfTSEN1, and showed potent anti-malarial activity against chloroquine-sensitive 3D7 and resistant strains Dd2 of P. falciparum. Overall, our study deliver key knowledge towards the functional role of PftRNA splicing endonuclease, and its inhibitor TSENi as potent anti-malarial.

molecular biology↗

bioRxiv2024

Tetra hydroxy ethyl disulfate disodium: a novel non-resistant antibacterial chelating agent

Discovery of novel antibacterial drugs is urgently required as common antibiotics have numerous side effects and are becoming less effective due to antibiotic resistance occurrences. Developing a novel class of antibacterial compounds without inducing the prevalence of resistance when used repeatedly against bacterial pathogens is presumably one of the best approaches to overcome this problem. Tetra hydroxy ethyl disulfate disodium (THES) is a novel antibacterial agent, capable of disrupting cell activity without any need for drug influx. In this study, the molecular interaction between THES, Gram-positive, and Gram-negative bacteria was investigated. It was suggested that THES possessed the desirable characteristics of a non-resistant bacterial agent with bactericidal properties. Additionally, the non-resistant characteristics of THES were validated as a novel antibacterial agent. The unique feature of THES was the property of chelation with its strong binding ability to target ligands. This binding played a major role in bacterial peptidoglycan porosity enlargement, resulting in lysis and cell death. The bacterial cell membrane porosity enlargement was confirmed by Scanning Electron Microscopy, Transmission Electron Microscopy, as well as Atomic Force Microscopy. These findings were further supported by the results from in silico analysis which showed that THES formed favorable interactions with peptidoglycan with a binding affinity of -4.7 kcal/mol. The minimum inhibitory concentration value against multidrug-resistant (MDR) bacteria was notably low, between 0.05 - 0.1%. Furthermore, the analysis of resistance over a seven-month course showed that Staphylococcus aureus did not develop resistant characteristics to repeated treatment to THES treatment. This study has also shown that bactericidal characteristics can be easily manipulated and modified for more preferable antibacterial activities, whilst yielding desirable pharmacokinetic/pharmacodynamics (PK/PD) properties. There are several advantages of THES as compared to common antibiotics, including its flexibility in the killing capacity of different microbial strains. The simplicity, efficacy, and non-resistant properties of THES make it a promising drug candidate or compound to combat the outbreak of MDR bacteria in the future.

biochemistry↗

bioRxiv2024

The reparative immunologic consequences of stem cell transplantation as a cellular therapy for refractory Crohn's disease

BackgroundTreatment strategies for Crohns disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous hematopoietic stem cell transplantation (SCT) has emerged as a therapy for medically refractory CD. SCT was developed to rescue cancer patients from myelosuppressive chemotherapy but its use for CD and other immune diseases necessitates reimagining SCT as a cellular therapy that restores appropriately responsive immune cell populations from hematopoietic progenitors in the stem cell autograft (i.e. immune "reset"). Here we present a paradigm to understand SCT as a cellular therapy for immune diseases and reveal how SCT re-establishes cellular immunity utilizing high-dimensional cellular phenotyping and functional studies of the stem cell grafts. MethodsImmunophenotyping using CyTOF, single cell RNA sequencing (scRNA-seq) and T cell receptor (TCR) sequencing was performed on peripheral blood and intestinal tissue samples from refractory CD patients who underwent SCT. The stem cell graft from these patients was analyzed using flow cytometry and functionally interrogated using a murine model for engraftment. ResultsOur study revealed a remodeling of intestinal macrophages capable of supporting mucosal healing that was independently validated using multimodal studies of immune reconstitution events including CyTOF and scRNA-seq. Functional interrogation of hematopoietic stem cells (HSCs) using a xenograft model demonstrated that HSCs shape the timing of immune reconstitution, the selected reconstitution of specific cell lineages and potentially the clinical efficacy of SCT. ConclusionsThese studies indicate that SCT serves as a myeloid-directed cellular therapy re-establishing homeostatic intestinal macrophages that support intestinal healing and suggest refractory CD evolves from impairment of restorative functions in myeloid cells. Furthermore, we report heterogeneity among HSCs from CD patients which may drive SCT outcomes and suggests an unrecognized impact of CD pathophysiology on HSC in the marrow niche.

immunology↗

bioRxiv2024

Obg-like ATPase 1 Genetic Deletion Leads to Dilated Cardiomyopathy in Mice and Structural Changes in Drosophila Heart

Cardiomyopathy, disease of the heart muscle, is a significant contributor to heart failure. The pathogenesis of cardiomyopathy is multifactorial and involves genetic, environmental, and lifestyle factors. Identifying and characterizing novel genes that contribute to cardiac pathophysiology are crucial for understanding cardiomyopathy and effective therapies. In this study, we investigated the role of a novel gene, Obg-like ATPase 1 (Ola1), in cardiac pathophysiology using a cardiac-specific knockout mouse model as well as a Drosophila model. Our previous work demonstrated that OLA1 modulates the hypertrophic response of cardiomyocytes through the GSK-beta/beta-catenin signaling pathway. Furthermore, recent studies have suggested that OLA1 plays a critical role in organismal growth and development. For example, Ola1 null mice exhibit increased heart size and growth retardation. It is not known, however, if loss of function for Ola1 leads to dilated cardiomyopathy. We generated cardiac-specific Ola1 knockout mice (OLA1-cKO) to evaluate the role of OLA1 in cardiac pathophysiology. We found that Ola1-cKO in mice leads to dilated cardiomyopathy (DCM) and left ventricular (LV) dysfunction. These mice developed severe LV dilatation, thinning of the LV wall, reduced LV function, and, in some cases, ventricular wall rupture and death. In Drosophila, RNAi-mediated knock-down specifically in developing heart cells led to the change in the structure of pericardial cells from round to elongated, and abnormal heart function. This also caused significant growth reduction and pupal lethality. Thus, our findings suggest that OLA1 is critical for cardiac homeostasis and that its deficiency leads to dilated cardiomyopathy and dysfunction. Furthermore, our study highlights the potential of the Ola1 gene as a therapeutic target for dilated cardiomyopathy and heart failure.

physiology↗

bioRxiv2024

SNX10 regulates the clearance of mitochondrial proteins and mitochondrial bioenergetics

We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy of OXPHOS machinery components. In control conditions, SNX10 localizes to early endocytic compartments in a PtdIns3P-dependent manner and modulates endosomal trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX- IV and SAMM50, and the autophagy proteins SQSTM1/p62 and LC3B. The turnover of COX-IV and the ATP synthase subunit pSu9 was enhanced in SNX10-depleted cells, with a corresponding reduced mitochondrial respiration and citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show reduced levels of COX-IV, as well as elevated ROS levels and ROS-mediated cell death in the brain, demonstrating the in vivo relevance of SNX10-mediated modulation of mitochondrial bioenergetics. eTOC summaryTrachsel-Moncho et al. identify the endosomal protein SNX10 as a modulator of piecemeal mitophagy of OXPHOS machinery components and mitochondrial homeostasis. They show that loss of SNX10 enhances mitochondrial protein degradation, reduces respiration, and increases ROS levels leading to elevated cell death in vivo.

cell biology↗

bioRxiv2024

A Decade in a Systematic Review: The Evolution and Impact of Cell Painting

High-content image-based assays have fueled significant discoveries in the life sciences in the past decade (2013-2023), including novel insights into disease etiology, mechanism of action, new therapeutics, and toxicology predictions. Here, we systematically review the substantial methodological advancements and applications of Cell Painting. Advancements include improvements in the Cell Painting protocol, assay adaptations for different types of perturbations and applications, and improved methodologies for feature extraction, quality control, and batch effect correction. Moreover, machine learning methods recently surpassed classical approaches in their ability to extract biologically useful information from Cell Painting images. Cell Painting data have been used alone or in combination with other - omics data to decipher the mechanism of action of a compound, its toxicity profile, and many other biological effects. Overall, key methodological advances have expanded Cell Paintings ability to capture cellular responses to various perturbations. Future advances will likely lie in advancing computational and experimental techniques, developing new publicly available datasets, and integrating them with other high-content data types.

cell biology↗