Biology subjects

Kadambat Nair, S.

Publications and source records attributed to Kadambat Nair, S..

3 recordsLinked to original sources

bioRxiv2023

GraphComm: A Graph-based Deep Learning Method to Predict Cell-Cell Communication in single-cell RNAseq data

Interactions between cells coordinate various functions across cell-types in health and disease states. Novel single-cell techniques enable deep investigation of cellular crosstalk at single-cell resolution. Cell-cell communication (CCC) is mediated by underlying gene-gene networks, however most current methods are unable to account for complex interactions within the cell as well as incorporate the effect of pathway and protein complexes on interactions. This results in the inability to infer overarching signalling patterns within a dataset as well as limit the ability to successfully explore other data types such as spatial cell dimension. Therefore, to represent transcriptomic data as intricate networks, complementing gene expression with information from cells to ligands and receptors for relevant cell-cell communication inference, we present GraphComm - a new graph-based deep learning method for predicting cell-cell communication in single-cell RNAseq datasets. GraphComm improves CCC inference by capturing detailed information such as cell location and intracellular signalling patterns from a database of more than 30,000 protein interaction pairs. With this framework, GraphComm is able to predict biologically relevant results in datasets previously validated for CCC, datasets that have undergone chemical or genetic perturbations and datasets with spatial cell information.

cell biology↗

bioRxiv2021

PharmacoDB 2.0 : Improving scalability and transparency of in vitro pharmacogenomics analysis

Cancer pharmacogenomics studies provide valuable insights into disease progression and associations between genomic features and drug response. PharmacoDB integrates multiple cancer pharmacogenomics datasets profiling approved and investigational drugs across cell lines from diverse tissue types. The web-application enables users to efficiently navigate across datasets, view and compare drug dose-response data for a specific drug-cell line pair. In the new version of PharmacoDB (version 2.0, https://pharmacodb.ca/), we present: (i) new datasets such as NCI-60, the Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) dataset, as well as updated data from the Genomics of Drug Sensitivity in Cancer (GDSC) and the Genentech Cell Line Screening Initiative (gCSI); (ii) implementation of FAIR data pipelines using ORCESTRA and PharmacoDI; (iii) enhancements to drug response analysis such as tissue distribution of dose-response metrics and biomarker analysis; (iv) improved connectivity to drug and cell line databases in the community. The web interface has been rewritten using a modern technology stack to ensure scalability and standardization to accommodate growing pharmacogenomics datasets. PharmacoDB 2.0 is a valuable tool for mining pharmacogenomics datasets, comparing and assessing drug response phenotypes of cancer models. HIGHLIGHTSO_LIPharmacoDB 2.0 includes new and updated large pharmacogenomic datasets. The data processing for PharmacoDB is made fully reproducible through the use of the ORCESTRA platform and automated data ingestion pipelines C_LIO_LIThe new release contains enriched annotations for drugs and cell lines via connectivity to external databases, as well as new analytical methods for tissue-specific and pan-cancer biomarker discovery C_LIO_LIThe new version of PharmacoDB incorporates a scalable and reproducible framework that can accelerate the implementation of analytical pipelines including machine learning/AI for biomarker discovery in the future C_LI

bioinformatics↗

bioRxiv2021

Drug Sensitivity Prediction From Cell Line-Based Pharmacogenomics Data: Guidelines for Developing Machine Learning Models

The goal of precision oncology is to tailor treatment for patients individually using the genomic profile of their tumors. Pharmacogenomics datasets such as cancer cell lines are among the most valuable resources for drug sensitivity prediction, a crucial task of precision oncology. Machine learning methods have been employed to predict drug sensitivity based on the multiple omics data available for large panels of cancer cell lines. However, there are no comprehensive guidelines on how to properly train and validate such machine learning models for drug sensitivity prediction. In this paper, we introduce a set of guidelines for different aspects of training gene expression-based predictors using cell line datasets. These guidelines provide extensive analysis of the generalization of drug sensitivity predictors, and challenge many current practices in the community including the choice of training dataset and measure of drug sensitivity. Application of these guidelines in future studies will enable the development of more robust preclinical biomarkers.

bioinformatics↗