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Biology subjects

Zagidullin, B.

Publications and source records attributed to Zagidullin, B..

3 recordsLinked to original sources

Interpretable prognostic modeling of endometrial cancer

Endometrial carcinoma (EC) is one of the most common gynecological cancers in the world. In this work we apply Cox proportional hazards (CPH) and optimal survival tree (OST) algorithms to the retrospective prognostic modeling of disease-specific survival in 842 EC patients. We demonstrate that the linear CPH models are preferred for the EC risk assessment based on clinical features alone, while the interpretable, non-linear OST models are favored when patient profiles are enriched with tumor molecular data. By studying the OST decision path structure, we show how explainable tree models recapitulate existing clinical knowledge prioritizing L1 cell-adhesion molecule and estrogen receptor status indicators as key risk factors in the p53 abnormal EC subgroup. We believe that visually interpretable tree algorithms are a promising method to explore feature interactions and generate novel research hypotheses. To aid further clinical adoption of advanced machine learning techniques, we stress the importance of quantifying model discrimination and calibration performance in the development of explainable clinical prediction models.

bioinformatics↗

Comparative analysis of molecular representations in prediction of cancer drug combination synergy and sensitivity

AO_SCPLOWBSTRACTC_SCPLOWApplication of machine and deep learning methods in drug discovery and cancer research has gained a considerable amount of attention in the past years. As the field grows, it becomes crucial to systematically evaluate the performance of novel computational solutions in relation to established techniques. To this end we compare rule-based and data-driven molecular representations in prediction of drug combination sensitivity and drug synergy scores using standardized results of 14 throughput screening studies, comprising 64 200 unique combinations of 4 153 molecules tested in 112 cancer cell lines. We evaluate the clustering performance of molecular representations and quantify their similarity by adapting the Centered Kernel Alignment metric. Our work demonstrates that to identify an optimal molecular representation type it is necessary to supplement quantitative benchmark results with qualitative considerations, such as model interpretability and robustness, which may vary between and throughout preclinical drug development projects. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/439299v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1bc4509org.highwire.dtl.DTLVardef@1586640org.highwire.dtl.DTLVardef@a11129org.highwire.dtl.DTLVardef@6dc93b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

DrugComb - an integrative cancer drug combination data portal

Drug combination therapy has the potential to enhance efficacy, reduce dose-dependent toxicity and prevent the emergence of drug resistance. However, discovery of synergistic and effective drug combinations has been a laborious and often serendipitous process. In recent years, identification of combination therapies has been accelerated due to the advances in high-throughput drug screening, but informatics approaches for systems-level data management and analysis are needed. To contribute toward this goal, we created an open-access data portal (https://drugcomb.fimm.fi) where the results of drug combination screening studies are accumulated, standardized and harmonized. Through the data portal, we provided the web server to analyze and visualize users own drug combination screening data. The users have an option to upload their data to DrugComb, as part of a crowdsourcing data curation effort. To initiate the data repository, we collected 437,932 drug combinations tested on a variety of cancer cell lines. We showed that linear regression approaches, when considering chemical fingerprints as predictors, have the potential to achieve high accuracy of predicting the sensitivity and synergy of drug combinations. All the data and informatics tools are freely available in DrugComb to enable a more efficient utilization of data resources for future drug combination discovery.

pharmacology and toxicology↗