Accurate drug response prediction (DRP) is a crucial yet challenging task in precision medicine. This paper presents a novel Attention-Guided Multi-omics Integration (AGMI) approach for DRP, which first constructs a Multi-edge Graph (MeG) for each cell line, and then aggregates multi-omics features to predict drug response using a novel structure, called Graph edge-aware Network (GeNet). For the first time, our AGMI approach explores gene constraint based multi-omics integration for DRP with the whole-genome using GNNs. Empirical experiments on the CCLE and GDSC datasets show that our AGMI largely outperforms state-of-the-art DRP methods by 8.3%--34.2% on four metrics. Our data and code are available at https://github.com/yivan-WYYGDSG/AGMI.
We propose the molecular omics network (MOOMIN) a multimodal graph neural network used by AstraZeneca oncologists to predict the synergy of drug combinations for cancer treatment. Our model learns drug representations at multiple scales based on a drug-protein interaction network and metadata. Structural properties of compounds and proteins are encoded to create vertex features for a message-passing scheme that operates on the bipartite interaction graph. Propagated messages form multi-resolution drug representations which we utilized to create drug pair descriptors. By conditioning the drug c…
DeepDTF: Dual-Branch Transformer Fusion for Multi-Omics Anticancer Drug Response Prediction
Department of Computer Science（计算机科学系）；North Carolina State University（北卡罗来纳州立大学）；UNC School of Medicine（UNC医学院）；University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）
Enhancing drug and cell line representations via contrastive learning for improved anti-cancer drug prioritization
The Ohio State University（俄亥俄州立大学）；Biomedical Informatics Department, The Ohio State University（俄亥俄州立大学生物医学信息学系）；Computer Science and Engineering Department, The Ohio State University（俄亥俄州立大学计算机科学与工程系）；Translational Data Analytics Institute, The Ohio State University（俄亥俄州立大学转化数据分析研究所）
TransCDR: a deep learning model for enhancing the generalizability of cancer drug response prediction through transfer learning and multimodal data fusion for drug representation
Shanghai Medical College, Fudan University（复旦大学上海医学院）；Shanghai Institute of Stem Cell Research and Clinical Translation（上海干细胞研究与临床转化研究院）；Shanghai World Foreign Language Academy（上海世界外国语中学）
Washington University School of Medicine, Washington University in St. Louis（圣路易斯华盛顿大学医学院）；Dalian University of Technology（大连理工大学）
Drug resistance is still a major challenge in cancer therapy. Drug combination is expected to overcome drug resistance. However, the number of possible drug combinations is enormous, and thus it is infeasible to experimentally screen all effective drug combinations considering the limited resources. Therefore, computational models to predict and prioritize effective drug combinations is important for combinatory therapy discovery in cancer. In this study, we proposed a novel deep learning model, AuDNNsynergy, to prediction drug combinations by integrating multi-omics data and chemical structur…
Identifying multi-omics interactions for lung cancer drug targets discovery using Kernel Machine Regression
Department of Information and Communication Technology, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Dhaka, Bangladesh（信息与通信技术系，穆拉纳巴沙尼科学与技术大学）；Department of Computer Science, Tulane University, New Orleans, LA, USA（计算机科学系，杜兰大学）；Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 138632, Singapore（生物信息学研究所（BII），科技研究局（A*STAR））；Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA 70112, USA（杜兰大学生物医学信息学与基因组学中心，医学部）；Ochsner Center for Outcomes Research, Ochsner Research, New Orleans, LA 70121, USA（Ochsner研究中心，Ochsner研究）
GRNFormer: A Biologically-Guided Framework for Integrating Gene Regulatory Networks into RNA Foundation Models
University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）；Rutgers University（罗格斯大学）；Barnard College（巴纳德学院）；Lawrence Livermore National Laboratory（劳伦斯利弗莫尔国家实验室）
A key challenge in systems biology is the elucidation of the underlying principles, or fundamental laws, which determine the cellular phenotype. Understanding how these fundamental principles are altered in diseases like cancer is important for translating basic scientific knowledge into clinical advances. While significant progress is being made, with the identification of novel drug targets and treatments by means of systems biological methods, our fundamental systems level understanding of why certain treatments succeed and others fail is still lacking. We here advocate a novel methodologic…
Aalto University（阿尔托大学）；University of Manchester（曼彻斯特大学）；Kyoto University（京都大学）
Detecting predictive biomarkers from multi-omics data is important for precision medicine, to improve diagnostics of complex diseases and for better treatments. This needs substantial experimental efforts that are made difficult by the heterogeneity of cell lines and huge cost. An effective solution is to build a computational model over the diverse omics data, including genomic, molecular, and environmental information. However, choosing informative and reliable data sources from among the different types of data is a challenging problem. We propose DIVERSE, a framework of Bayesian importance…
High-confidence prediction of complex traits such as disease risk or drug response is an ultimate goal of personalized medicine. Although genome-wide association studies have discovered thousands of well-replicated polymorphisms associated with a broad spectrum of complex traits, the combined predictive power of these associations for any given trait is generally too low to be of clinical relevance. We propose a novel systems approach to complex trait prediction, which leverages and integrates similarity in genetic, transcriptomic or other omics-level data. We translate the omic similarity int…
City University of New York（纽约城市大学）；Hunter College, City University of New York（纽约城市大学亨特学院）
An unsolved fundamental problem in biology and ecology is to predict observable traits (phenotypes) from a new genetic constitution (genotype) of an organism under environmental perturbations (e.g., drug treatment). The emergence of multiple omics data provides new opportunities but imposes great challenges in the predictive modeling of genotype-phenotype associations. Firstly, the high-dimensionality of genomics data and the lack of labeled data often make the existing supervised learning techniques less successful. Secondly, it is a challenging task to integrate heterogeneous omics data from…
With the advancements in Artificial intelligence (AI) and the accumulation of healthrelated big data, it has become increasingly feasible and commonplace to leverage machine learning technologies to analyze clinical and omics metadata to assess the possibility of adverse drug reactions or events (ADRs) in the course of drug discovery. Here, we have described a novel approach that combined drug-induced gene expression profile from Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation Systems) and ADR occurrence information from FAERS (FDA [Food and Drug Administration] Adv…
Graduate Center, City University of New York（纽约城市大学研究生中心）；Feil Family Brain & Mind Research Institute, Weill Cornell Medicine, Cornell University（康奈尔大学威尔康奈尔医学院菲尔家族脑与心智研究所）；Hunter College, City University of New York（纽约城市大学亨特学院）
Accurate and robust prediction of patient's response to drug treatments is critical for developing precision medicine. However, it is often difficult to obtain a sufficient amount of coherent drug response data from patients directly for training a generalized machine learning model. Although the utilization of rich cell line data provides an alternative solution, it is challenging to transfer the knowledge obtained from cell lines to patients due to various confounding factors. Few existing transfer learning methods can reliably disentangle common intrinsic biological signals from confounding…
TOBB University of Economics and Technology（TOBB经济与技术大学）；Hacettepe University（哈塞特佩大学）
Chemotherapeutic response of cancer cells to a given compound is one of the most fundamental information one requires to design anti-cancer drugs. Recent advances in producing large drug screens against cancer cell lines provided an opportunity to apply machine learning methods for this purpose. In addition to cytotoxicity databases, considerable amount of drug-induced gene expression data has also become publicly available. Following this, several methods that exploit omics data were proposed to predict drug activity on cancer cells. However, due to the complexity of cancer drug mechanisms, n…
The organization and mining of malaria genomic and post-genomic data is highly motivated by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should therefore be as reliable and versatile as possible. In this context, we examined five aspects o…
Motivation: The consistent amount of different types of omics data requires novel methods of analysis and data integration. In this work we describe Regression2Net, a computational approach to analyse gene expression and methylation profiles via regression analysis and network-based techniques. Results: We identified 284 and 447 unique candidate genes potentially associated to the Glioblastoma pathology from two networks inferred from mixed genetic datasets. In-depth biological analysis of these networks reveals genes that are related to energy metabolism, cell cycle control (AATF), immune sys…
