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 therapeutic target


Learning Identifiable Factorized Causal Representations of Cellular Responses

Neural Information Processing Systems

The study of cells and their responses to genetic or chemical perturbations promises to accelerate the discovery of therapeutics targets. However, designing adequate and insightful models for such data is difficult because the response of a cell to perturbations essentially depends on contextual covariates (e.g., genetic background or type of the cell). There is therefore a need for models that can identify interactions between drugs and contextual covariates. This is crucial for discovering therapeutics targets, as such interactions may reveal drugs that affect certain cell types but not others.We tackle this problem with a novel Factorized Causal Representation (FCR) learning method, an identifiable deep generative model that reveals causal structure in single-cell perturbation data from several cell lines. FCR learns multiple cellular representations that are disentangled, comprised of covariate-specific (Z t) and interaction-specific (Z tx and block-wise identifiability of Z x. Then, we present our implementation of FCR, and empirically demonstrate that FCR outperforms state-of-the-art baselines in various tasks across four single-cell datasets.


Utilizing the RAIN method and Graph SAGE Model to Identify Effective Drug Combinations for Gastric Neoplasm Treatment

arXiv.org Artificial Intelligence

Background: Gastric neoplasm, primarily adenocarcinoma, is an aggressive cancer with high mortality, often diagnosed late, leading to complications like metastasis. Effective drug combinations are vital to address disease heterogeneity, enhance efficacy, reduce resistance, and improve patient outcomes. Methods: The RAIN method integrated Graph SAGE to propose drug combinations, using a graph model with p-value-weighted edges connecting drugs, genes, and proteins. NLP and systematic literature review (PubMed, Scopus, etc.) validated proposed drugs, followed by network meta-analysis to assess efficacy, implemented in Python. Results: Oxaliplatin, fluorouracil, and trastuzumab were identified as effective, supported by 61 studies. Fluorouracil alone had a p-value of 0.0229, improving to 0.0099 with trastuzumab, and 0.0069 for the triple combination, indicating superior efficacy. Conclusion: The RAIN method, combining AI and network meta-analysis, effectively identifies optimal drug combinations for gastric neoplasm, offering a promising strategy to enhance treatment outcomes and guide health policy.


Learning Identifiable Factorized Causal Representations of Cellular Responses

Neural Information Processing Systems

The study of cells and their responses to genetic or chemical perturbations promises to accelerate the discovery of therapeutics targets. However, designing adequate and insightful models for such data is difficult because the response of a cell to perturbations essentially depends on contextual covariates (e.g., genetic background or type of the cell). There is therefore a need for models that can identify interactions between drugs and contextual covariates. This is crucial for discovering therapeutics targets, as such interactions may reveal drugs that affect certain cell types but not others.We tackle this problem with a novel Factorized Causal Representation (FCR) learning method, an identifiable deep generative model that reveals causal structure in single-cell perturbation data from several cell lines. FCR learns multiple cellular representations that are disentangled, comprised of covariate-specific (Zx), treatment-specific (Zt) and interaction-specific (Ztx) representations.


Machine Learning-Based Prediction of Key Genes Correlated to the Subretinal Lesion Severity in a Mouse Model of Age-Related Macular Degeneration

arXiv.org Artificial Intelligence

Age-related macular degeneration (AMD) is a major cause of blindness in older adults, severely affecting vision and quality of life. Despite advances in understanding AMD, the molecular factors driving the severity of subretinal scarring (fibrosis) remain elusive, hampering the development of effective therapies. This study introduces a machine learning-based framework to predict key genes that are strongly correlated with lesion severity and to identify potential therapeutic targets to prevent subretinal fibrosis in AMD. Using an original RNA sequencing (RNA-seq) dataset from the diseased retinas of JR5558 mice, we developed a novel and specific feature engineering technique, including pathway-based dimensionality reduction and gene-based feature expansion, to enhance prediction accuracy. Two iterative experiments were conducted by leveraging Ridge and ElasticNet regression models to assess biological relevance and gene impact. The results highlight the biological significance of several key genes and demonstrate the framework's effectiveness in identifying novel therapeutic targets. The key findings provide valuable insights for advancing drug discovery efforts and improving treatment strategies for AMD, with the potential to enhance patient outcomes by targeting the underlying genetic mechanisms of subretinal lesion development.


Artificial intelligence (AI) and big data in cancer and precision oncology

#artificialintelligence

Artificial intelligence (AI) and machine learning have significantly influenced many facets of the healthcare sector. Advancement in technology has paved the way for analysis of big datasets in a cost- and time-effective manner. Clinical oncology and research are reaping the benefits of AI. The burden of cancer is a global phenomenon. Efforts to reduce mortality rates requires early diagnosis for effective therapeutic interventions.


Identifying protein targets in SARS-CoV-2 via machine learning

#artificialintelligence

The coronavirus disease 2019 (COVID-19) pandemic has affected nearly 271 million people and has claimed 5.32 million lives, the most recent episode being of the delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic just adds to the list of infectious diseases that were potential global threats like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola, and Zika. Infections like these highlight the need for the development of therapeutic agents to combat emerging pathogens. The process of developing therapeutic solutions to novel viruses is tedious and prohibitively long, taking up to 10 to 15 years of time. The initial step of determining interesting molecules and therapeutic targets for further investigation is crucial due to the vast size of the chemical space, which prevents an exhaustive search using costly experiments and trials.