Background Survival and drug response are two highly emphasized clinical outcomes in cancer research that directs the prognosis of a cancer patient. Here, we have proposed a late multi omics integrative framework that robustly quantifies survival and drug response for breast cancer patients with a focus on the relative predictive ability of available omics datatypes. Neighborhood component analysis (NCA), a supervised feature selection algorithm selected relevant features from multi-omics datasets retrieved from The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases. A Neural network framework, fed with NCA selected features, was used to develop survival and drug response prediction models for breast cancer patients. The drug response framework used regression and unsupervised clustering (K-means) to segregate samples into responders and non-responders based on their predicted IC50 values (Z-score). Results The survival prediction framework was highly effective in categorizing patients into risk subtypes with an accuracy of 94%. Compared to single-omics and early integration approaches, our drug response prediction models performed significantly better and were able to predict IC50 values (Z-score) with a mean square error (MSE) of 1.154 and an overall regression value of 0.92, showing a linear relationship between predicted and actual IC50 values. Conclusion The proposed omics integration strategy provides an effective way of extracting critical information from diverse omics data types enabling estimation of prognostic indicators. Such integrative models with high predictive power would have a significant impact and utility in precision oncology.
The identification of novel drug–target interactions is a labor-intensive and low-throughput process. In silico alternatives have proved to be of immense importance in assisting the drug discovery process. Here, we present TransDTI, a multiclass classification and regression workflow employing transformer-based language models to segregate interactions between drug–target pairs as active, inactive, and intermediate. The models were trained with large-scale drug–target interaction (DTI) data sets, which reported an improvement in performance in terms of the area under receiver operating characteristic (auROC), the area under precision recall (auPR), Matthew’s correlation coefficient (MCC), and R2 over baseline methods. The results showed that models based on transformer-based language models effectively predict novel drug–target interactions from sequence data. The proposed models significantly outperformed existing methods like DeepConvDTI, DeepDTA, and DeepDTI on a test data set. Further, the validity of novel interactions predicted by TransDTI was found to be backed by molecular docking and simulation analysis, where the model prediction had similar or better interaction potential for MAP2k and transforming growth factor-β (TGFβ) and their known inhibitors. Proposed approaches can have a significant impact on the development of personalized therapy and clinical decision making.
In silico methods to identify novel drug–target interactions (DTIs) have gained significant importance over conventional techniques owing to their labor-intensive and low-throughput nature. Here, we present a machine learning-based multiclass classification workflow that segregates interactions between active, inactive, and intermediate drug–target pairs. Drug molecules, protein sequences, and molecular descriptors were transformed into machine-interpretable embeddings to extract critical features from standard datasets. Tools such as CHEMBL web resource, iFeature, and an in-house developed deep neural network-assisted drug recommendation (dNNDR)-featx were employed for data retrieval and processing. The models were trained with large-scale DTI datasets, which reported an improvement in performance over baseline methods. External validation results showed that models based on att-biLSTM and gCNN could help predict novel DTIs. When tested with a completely different dataset, the proposed models significantly outperformed competing methods. The validity of novel interactions predicted by dNNDR was backed by experimental and computational evidence in the literature. The proposed methodology could elucidate critical features that govern the relationship between a drug and its target.
The utility of multi-omics in personalized therapy and cancer survival analysis has been debated and demonstrated extensively in the recent past. Most of the current methods still suffer from data constraints such as high-dimensionality, unexplained interdependence, and subpar integration methods. Here, we propose SurvCNN, an alternative approach to process multi-omics data with robust computer vision architectures, to predict cancer prognosis for Lung Adenocarcinoma patients. Numerical multi-omics data were transformed into their image representations and fed into a Convolutional Neural network with a discrete-time model to predict survival probabilities. The framework also dichotomized patients into risk subgroups based on their survival probabilities over time. SurvCNN was evaluated on multiple performance metrics and outperformed existing methods with a high degree of confidence. Moreover, comprehensive insights into the relative performance of various combinations of omics datasets were probed. Critical biological processes, pathways and cell types identified from downstream processing of differentially expressed genes suggested that the framework could elucidate elements detrimental to a patient’s survival. Such integrative models with high predictive power would have a significant impact and utility in precision oncology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.