Federated Ensemble Regression Using Classification

Ensemble learning has been shown to significantly improve predictive accuracy in a variety of machine learning problems. For a given predictive task, the goal of ensemble learning is to improve predictive accuracy by combining the predictive power of multiple models. In this paper, we present an ensemble learning algorithm for regression problems which leverages the distribution of the samples in a learning set to achieve improved performance. We apply the proposed algorithm to a problem in precision medicine where the goal is to predict drug perturbation effects on genes in cancer cell lines. The proposed approach significantly outperforms the base case

Generating Explainable and Effective Data Descriptors Using Relational Learning: Application to Cancer Biology

The key to success in machine learning is the use of effective data representations. The success of deep neural networks (DNNs) is based on their ability to utilize multiple neural network layers, and big data, to learn how to convert simple input representations into richer internal representations that are effective for learning. However, these internal representations are sub-symbolic and difficult to explain. In many scientific problems explainable models are required, and the input data is semantically complex and unsuitable for DNNs. This is true in the fundamental problem of understanding the mechanism of cancer drugs, which requires complex background knowledge about the functions of genes/proteins, their cells, and the molecular structure of the drugs. This background knowledge cannot be compactly expressed propositionally, and requires at least the expressive power of Datalog. Here we demonstrate the use of relational learning to generate new data descriptors in such semantically complex background knowledge. These new descriptors are effective: adding them to standard propositional learning methods significantly improves prediction accuracy. They are also explainable, and add to our understanding of cancer. Our approach can readily be expanded to include other complex forms of background knowledge, and combines the generality of relational learning with the efficiency of standard propositional learning

Evolving BioAssay Ontology (BAO): modularization, integration and applications

The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project ( http://bioassayontology.org ) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and datasets

Datasets2Tools, repository and search engine for bioinformatics datasets, tools and canned analyses

Biomedical data repositories such as the Gene Expression Omnibus (GEO) enable the search and discovery of relevant biomedical digital data objects. Similarly, resources such as OMICtools, index bioinformatics tools that can extract knowledge from these digital data objects. However, systematic access to pre-generated ‘canned’ analyses applied by bioinformatics tools to biomedical digital data objects is currently not available. Datasets2Tools is a repository indexing 31,473 canned bioinformatics analyses applied to 6,431 datasets. The Datasets2Tools repository also contains the indexing of 4,901 published bioinformatics software tools, and all the analyzed datasets. Datasets2Tools enables users to rapidly find datasets, tools, and canned analyses through an intuitive web interface, a Google Chrome extension, and an API. Furthermore, Datasets2Tools provides a platform for contributing canned analyses, datasets, and tools, as well as evaluating these digital objects according to their compliance with the findable, accessible, interoperable, and reusable (FAIR) principles. By incorporating community engagement, Datasets2Tools promotes sharing of digital resources to stimulate the extraction of knowledge from biomedical research data. Datasets2Tools is freely available from: http://amp.pharm.mssm.edu/datasets2tools

FAIR LINCS Data and Metadata powered by the CEDAR Framework

The Library of Integrated Network-based Signatures (LINCS) program generates a wide variety of cell-based perturbation-response signatures using diverse assay technologies. For example, LINCS includes large-scale transcriptional profiling of genetic and small molecule perturbations, and various proteomics and imaging datasets. We have developed data processing pipelines, and supporting informatics infrastructure to access, standardize and harmonize, register and publish LINCS datasets and metadata from all Data and Signature Generating Centers (DSGC’s). Metadata standards specifications provide a foundation for harmonizing and integrating LINCS data. Here we introduce a CEDAR-based LINCS Community Metadata Environment, to support end-to-end metadata management framework that supports authoring, curation, validation, management, and sharing of LINCS metadata, while building upon the existing LINCS metadata standards and data-release workflows. Following this initial validation, our goal is to create reusable metadata modules with user friendly templates for each of the LINCS metadata categories and to make our suite of tools compatible with the CEDAR metadata technologies. This should further simplify metadata handling in the LINCS consortium and facilitate a global metadata repository at CEDAR. As other projects apply the same approach, many more datasets will become cross-searchable and can be linked optimizing the metadata pathway from submission to discovery

Connecting omics signatures and revealing biological mechanisms with iLINCS

There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here we present iLINCS (http://ilincs.org), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The platform facilitates mining and re-analysis of the large collection of omics datasets (>34,000), pre-computed signatures (>200,000), and their connections, as well as the analysis of user-submitted omics signatures of diseases and cellular perturbations. iLINCS analysis workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. iLINCS user-friendly interfaces enable execution of sophisticated analyses of omics signatures, mechanism of action analysis, and signature-driven drug repositioning. We illustrate the utility of iLINCS with three use cases involving analysis of cancer proteogenomic signatures, COVID 19 transcriptomic signatures and mTOR signaling. There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here the authors present an integrative web-based platform for analysis of omics data and signatures of cellular perturbations