From patterned response dependency to structured covariate dependency: categorical-pattern-matching

Data generated from a system of interest typically consists of measurements from an ensemble of subjects across multiple response and covariate features, and is naturally represented by one response-matrix against one covariate-matrix. Likely each of these two matrices simultaneously embraces heterogeneous data types: continuous, discrete and categorical. Here a matrix is used as a practical platform to ideally keep hidden dependency among/between subjects and features intact on its lattice. Response and covariate dependency is individually computed and expressed through mutliscale blocks via a newly developed computing paradigm named Data Mechanics. We propose a categorical pattern matching approach to establish causal linkages in a form of information flows from patterned response dependency to structured covariate dependency. The strength of an information flow is evaluated by applying the combinatorial information theory. This unified platform for system knowledge discovery is illustrated through five data sets. In each illustrative case, an information flow is demonstrated as an organization of discovered knowledge loci via emergent visible and readable heterogeneity. This unified approach fundamentally resolves many long standing issues, including statistical modeling, multiple response, renormalization and feature selections, in data analysis, but without involving man-made structures and distribution assumptions. The results reported here enhance the idea that linking patterns of response dependency to structures of covariate dependency is the true philosophical foundation underlying data-driven computing and learning in sciences.Comment: 32 pages, 10 figures, 3 box picture

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Computational structure‐based drug design: Predicting target flexibility

The role of molecular modeling in drug design has experienced a significant revamp in the last decade. The increase in computational resources and molecular models, along with software developments, is finally introducing a competitive advantage in early phases of drug discovery. Medium and small companies with strong focus on computational chemistry are being created, some of them having introduced important leads in drug design pipelines. An important source for this success is the extraordinary development of faster and more efficient techniques for describing flexibility in three‐dimensional structural molecular modeling. At different levels, from docking techniques to atomistic molecular dynamics, conformational sampling between receptor and drug results in improved predictions, such as screening enrichment, discovery of transient cavities, etc. In this review article we perform an extensive analysis of these modeling techniques, dividing them into high and low throughput, and emphasizing in their application to drug design studies. We finalize the review with a section describing our Monte Carlo method, PELE, recently highlighted as an outstanding advance in an international blind competition and industrial benchmarks.We acknowledge the BSC-CRG-IRB Joint Research Program in Computational Biology. This work was supported by a grant from the Spanish Government CTQ2016-79138-R.J.I. acknowledges support from SVP-2014-068797, awarded by the Spanish Government.Peer ReviewedPostprint (author's final draft

Statistical modeling of RNA structure profiling experiments enables parsimonious reconstruction of structure landscapes.

RNA plays key regulatory roles in diverse cellular processes, where its functionality often derives from folding into and converting between structures. Many RNAs further rely on co-existence of alternative structures, which govern their response to cellular signals. However, characterizing heterogeneous landscapes is difficult, both experimentally and computationally. Recently, structure profiling experiments have emerged as powerful and affordable structure characterization methods, which improve computational structure prediction. To date, efforts have centered on predicting one optimal structure, with much less progress made on multiple-structure prediction. Here, we report a probabilistic modeling approach that predicts a parsimonious set of co-existing structures and estimates their abundances from structure profiling data. We demonstrate robust landscape reconstruction and quantitative insights into structural dynamics by analyzing numerous data sets. This work establishes a framework for data-directed characterization of structure landscapes to aid experimentalists in performing structure-function studies

A General Spatio-Temporal Clustering-Based Non-local Formulation for Multiscale Modeling of Compartmentalized Reservoirs

Representing the reservoir as a network of discrete compartments with neighbor and non-neighbor connections is a fast, yet accurate method for analyzing oil and gas reservoirs. Automatic and rapid detection of coarse-scale compartments with distinct static and dynamic properties is an integral part of such high-level reservoir analysis. In this work, we present a hybrid framework specific to reservoir analysis for an automatic detection of clusters in space using spatial and temporal field data, coupled with a physics-based multiscale modeling approach. In this work a novel hybrid approach is presented in which we couple a physics-based non-local modeling framework with data-driven clustering techniques to provide a fast and accurate multiscale modeling of compartmentalized reservoirs. This research also adds to the literature by presenting a comprehensive work on spatio-temporal clustering for reservoir studies applications that well considers the clustering complexities, the intrinsic sparse and noisy nature of the data, and the interpretability of the outcome. Keywords: Artificial Intelligence; Machine Learning; Spatio-Temporal Clustering; Physics-Based Data-Driven Formulation; Multiscale Modelin