Unlocking the Potential of Kinase Targets in Cancer: Insights from CancerOmicsNet, an AI-Driven Approach to Drug Response Prediction in Cancer.

Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases.

Artificial intelligence to guide precision anticancer therapy with multitargeted kinase inhibitors.

Background: Vast amounts of rapidly accumulating biological data related to cancer and a remarkable progress in the field of artificial intelligence (AI) have paved the way for precision oncology. Our recent contribution to this area of research is CancerOmicsNet, an AI-based system to predict the therapeutic effects of multitargeted kinase inhibitors across various cancers. This approach was previously demonstrated to outperform other deep learning methods, graph kernel models, molecular docking, and drug binding pocket matching.

GraphSite: Ligand Binding Site Classification with Deep Graph Learning.

The binding of small organic molecules to protein targets is fundamental to a wide array of cellular functions. It is also routinely exploited to develop new therapeutic strategies against a variety of diseases. On that account, the ability to effectively detect and classify ligand binding sites in proteins is of paramount importance to modern structure-based drug discovery.

CancerOmicsNet: a multi-omics network-based approach to anti-cancer drug profiling.

Development of novel anti-cancer treatments requires not only a comprehensive knowledge of cancer processes and drug mechanisms of action, but also the ability to accurately predict the response of various cancer cell lines to therapeutics. Numerous computational methods have been developed to address this issue, including algorithms employing supervised machine learning. Nonetheless, high prediction accuracies reported for many of these techniques may result from a significant overlap among training, validation, and testing sets, making existing predictors inapplicable to new data.

An integrated network representation of multiple cancer-specific data for graph-based machine learning.

Genomic profiles of cancer cells provide valuable information on genetic alterations in cancer. Several recent studies employed these data to predict the response of cancer cell lines to drug treatment. Nonetheless, due to the multifactorial phenotypes and intricate mechanisms of cancer, the accurate prediction of the effect of pharmacotherapy on a specific cell line based on the genetic information alone is problematic.

Pocket2Drug: An Encoder-Decoder Deep Neural Network for the Target-Based Drug Design.

Computational modeling is an essential component of modern drug discovery. One of its most important applications is to select promising drug candidates for pharmacologically relevant target proteins. Because of continuing advances in structural biology, putative binding sites for small organic molecules are being discovered in numerous proteins linked to various diseases.

GraphDTI: A robust deep learning predictor of drug-target interactions from multiple heterogeneous data.

Traditional techniqueset identification, we developed GraphDTI, a robust machine learning framework integrating the molecular-level information on drugs, proteins, and binding sites with the system-level information on gene expression and protein-protein interactions. In order to properly evaluate the performance of GraphDTI, we compiled a high-quality benchmarking dataset and devised a new cluster-based cross-validation p to identify macromolecular targets for drugs utilize solely the information on a query drug and a putative target. Nonetheless, the mechanisms of action of many drugs depend not only on their binding affinity toward a single protein, but also on the signal transduction through cascades of molecular interactions leading to certain phenotypes.

BionoiNet: ligand-binding site classification with off-the-shelf deep neural network.

Motivation: Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide- and heme-binding sites with a comparable accuracy to highly specialized, voxel-based methods.

Large-scale computational drug repositioning to find treatments for rare diseases.

Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.