SynerGNet: A Graph Neural Network Model to Predict Anticancer Drug Synergy.

Drug combination therapy shows promise in cancer treatment by addressing drug resistance, reducing toxicity, and enhancing therapeutic efficacy. However, the intricate and dynamic nature of biological systems makes identifying potential synergistic drugs a costly and time-consuming endeavor. To facilitate the development of combination therapy, techniques employing artificial intelligence have emerged as a transformative solution, providing a sophisticated avenue for advancing existing therapeutic approaches.

Augmented drug combination dataset to improve the performance of machine learning models predicting synergistic anticancer effects.

Combination therapy has gained popularity in cancer treatment as it enhances the treatment efficacy and overcomes drug resistance. Although machine learning (ML) techniques have become an indispensable tool for discovering new drug combinations, the data on drug combination therapy currently available may be insufficient to build high-precision models. We developed a data augmentation protocol to unbiasedly scale up the existing anti-cancer drug synergy dataset.

Augmented drug combination dataset to improve the performance of machine learning models predicting synergistic anticancer effects.

Combination therapy has gained popularity in cancer treatment as it enhances the treatment efficacy and overcomes drug resistance. Although machine learning (ML) techniques have become an indispensable tool for discovering new drug combinations, the data on drug combination therapy currently available may be insufficient to build high-precision models. We developed a data augmentation protocol to unbiasedly scale up the existing anti-cancer drug synergy dataset.

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.

Bionoi: A Voronoi Diagram-Based Representation of Ligand-Binding Sites in Proteins for Machine Learning Applications.

Bionoi is a new software to generate Voronoi representations of ligand-binding sites in proteins for machine learning applications. Unlike many other deep learning models in biomedicine, Bionoi utilizes off-the-shelf convolutional neural network architectures, reducing the development work without sacrificing the performance. When initially generating images of binding sites, users have the option to color the Voronoi cells based on either one of six structural, physicochemical, and evolutionary properties, or a blend of all six individual properties.

Strengthening spatial reasoning: elucidating the attentional and neural mechanisms associated with mental rotation skill development.

Spatial reasoning is a critical skill in many everyday tasks and in science, technology, engineering, and mathematics disciplines. The current study examined how training on mental rotation (a spatial reasoning task) impacts the completeness of an encoded representation and the ability to rotate the representation. We used a multisession, multimethod design with an active control group to determine how mental rotation ability impacts performance for a trained stimulus category and an untrained stimulus category.

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.

Performance characteristics of recycled concrete aggregate as an unbound pavement material.

Use of recycled concrete aggregates (RCA) as a pavement material is one of the most sustainable engineering applications for the pavement industry. Investigation on the performance characteristics of RCA, such as elastic and plastic deformations of RCA is therefore, needed to assess RCA's application as an unbound pavement material. In this study, repeated load tri-axial (RLT) tests were conducted to investigate the response of RCA to elastic and plastic deformations under dynamic loads.

Identifying Sentiment of Hookah-Related Posts on Twitter.

Background: The increasing popularity of hookah (or waterpipe) use in the United States and elsewhere has consequences for public health because it has similar health risks to that of combustible cigarettes. While hookah use rapidly increases in popularity, social media data (Twitter, Instagram) can be used to capture and describe the social and environmental contexts in which individuals use, perceive, discuss, and are marketed this tobacco product. These data may allow people to organically report on their sentiment toward tobacco products like hookah unprimed by a researcher, without instrument bias, and at low costs.

Assessing the similarity of ligand binding conformations with the Contact Mode Score.

Structural and computational biologists often need to measure the similarity of ligand binding conformations. The commonly used root-mean-square deviation (RMSD) is not only ligand-size dependent, but also may fail to capture biologically meaningful binding features. To address these issues, we developed the Contact Mode Score (CMS), a new metric to assess the conformational similarity based on intermolecular protein-ligand contacts.

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening.

GeauxDock: A novel approach for mixed-resolution ligand docking using a descriptor-based force field.

Molecular docking is an important component of computer-aided drug discovery. In this communication, we describe GeauxDock, a new docking approach that builds on the ideas of ligand homology modeling. GeauxDock features a descriptor-based scoring function integrating evolutionary constraints with physics-based energy terms, a mixed-resolution molecular representation of protein-ligand complexes, and an efficient Monte Carlo sampling protocol.

Psychiatric morbidity among prisoners.

Background: There is a considerable lack of scientific estimate of psychiatric morbidity among Indian prisoners.

Objective: The objective of the following study is to study the prevalence of psychiatric morbidity among prisoners.

Settings And Design: A cross-sectional study at District Jail, Kozhikode, Kerala.

Solving the parquet equations for the Hubbard model beyond weak coupling.

We find that imposing crossing symmetry in the iteration process considerably extends the range of convergence for solutions of the parquet equations for the Hubbard model. When crossing symmetry is not imposed, the convergence of both simple iteration and more complicated continuous loading (homotopy) methods is limited to high temperatures and weak interactions. We modify the algorithm to impose the crossing symmetry without increasing the computational complexity.

Performance optimization of tensor contraction expressions for many-body methods in quantum chemistry.

Complex tensor contraction expressions arise in accurate electronic structure models in quantum chemistry, such as the coupled cluster method. This paper addresses two complementary aspects of performance optimization of such tensor contraction expressions. Transformations using algebraic properties of commutativity and associativity can be used to significantly decrease the number of arithmetic operations required for evaluation of these expressions.

A neural architecture for a class of abduction problems.

The general task of abduction is to infer a hypothesis that best explains a set of data. A typical subtask of this is to synthesize a composite hypothesis that best explains the entire data from elementary hypotheses which can explain portions of it. The synthesis subtask of abduction is computationally expensive, more so in the presence of certain types of interactions between the elementary hypotheses.