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Mathematical models in systems biology help generate hypotheses, guide experimental design, and infer the dynamics of gene regulatory networks. These models are characterized by phenomenological or mechanistic parameters, which are typically hard to measure. Therefore, efficient parameter estimation is central to model development. Global optimization techniques, such as evolutionary algorithms (EAs), are applied to estimate model parameters by inverse modeling, i.e. calibrating models by minimizing a function that evaluates a measure of the error between model predictions and experimental data. EAs estimate model parameters “fittest individuals” by generating a large population of individuals using strategies like recombination and mutation over multiple “generations.” Typically, only a few individuals from each generation are used to create new individuals in the next generation. Improved Evolutionary Strategy by Stochastic Ranking (ISRES), proposed by Runnarson and Yao, is one such EA that is widely used in systems biology to estimate parameters. ISRES uses information at most from a pair of individuals in any generation to create a new population to minimize the error. In this article, we propose an efficient evolutionary strategy, ISRES+, which builds on ISRES by combining information from all individuals across the population and across all generations to develop a better understanding of the fitness landscape.

ISRES+ uses the additional information generated by the algorithm during evolution to approximate the local neighborhood around the best-fit individual using linear least squares fits in one and two dimensions, enabling efficient parameter estimation. ISRES+ outperforms ISRES and results in fitter individuals with a tighter distribution over multiple runs, such that a typical run of ISRES+ estimates parameters with a higher goodness-of-fit compared with ISRES.

Algorithm and implementation: Github—https://github.com/gtreeves/isres-plus-bandodkar-2022.

 

Abstract Motivation In the training of predictive models using high-dimensional genomic data, multiple studies’ worth of data are often combined to increase sample size and improve generalizability. A drawback of this approach is that there may be different sets of features measured in each study due to variations in expression measurement platform or technology. It is often common practice to work only with the intersection of features measured in common across all studies, which results in the blind discarding of potentially useful feature information that is measured in individual or subsets of studies. Results We characterize the loss in predictive performance incurred by using only the intersection of feature information available across all studies when training predictors using gene expression data from microarray and sequencing datasets. We study the properties of linear and polynomial regression for imputing discarded features and demonstrate improvements in the external performance of prediction functions through simulation and in gene expression data collected on breast cancer patients. To improve this process, we propose a pairwise strategy that applies any imputation algorithm to two studies at a time and averages imputed features across pairs. We demonstrate that the pairwise strategy is preferable to first merging all datasets together and imputing any resulting missing features. Finally, we provide insights on which subsets of intersected and study-specific features should be used so that missing-feature imputation best promotes cross-study replicability. Availability and implementation The code is available at https://github.com/YujieWuu/Pairwise_imputation. Supplementary information Supplementary information is available at Bioinformatics online. 

Abstract Motivation Substance abuse constitutes one of the major contemporary health epidemics. Recently, the use of social media platforms has garnered interest as a novel source of data for drug addiction epidemiology. Often however, the language used in such forums comprises slang and jargon. Currently, there are no publicly available resources to automatically analyse the esoteric language-use in the social media drug-use sub-culture. This lacunae introduces critical challenges for interpreting, sensemaking and modeling of addiction epidemiology using social media. Results Drug-Use Insights (DUI) is a public and open-source web application to address the aforementioned deficiency. DUI is underlined by a hierarchical taxonomy encompassing 108 different addiction related categories consisting of over 9,000 terms, where each category encompasses a set of semantically related terms. These categories and terms were established by utilizing thematic analysis in conjunction with term embeddings generated from 7,472,545 Reddit posts made by 1,402,017 redditors. Given post(s) from social media forums such as Reddit and Twitter, DUI can be used foremost to identify constituent terms related to drug use. Furthermore, the DUI categories and integrated visualization tools can be leveraged for semantic- and exploratory analysis. To the best of our knowledge, DUI utilizes the largest number of substance use and recovery social media posts used in a study and represents the first significant online taxonomy of drug abuse terminology. Availability The DUI web server and source code are available at: http://haddock9.sfsu.edu/insight/ Supplementary information Supplementary data are available at Bioinformatics online. 

Abstract Motivation The discovery of biologically interpretable and clinically actionable communities in heterogeneous omics data is a necessary first step toward deriving mechanistic insights into complex biological phenomena. Here, we present a novel clustering approach, omeClust, for community detection in omics profiles by simultaneously incorporating similarities among measurements and the overall complex structure of the data. Results We show that omeClust outperforms published methods in inferring the true community structure as measured by both sensitivity and misclassification rate on simulated datasets. We further validated omeClust in diverse, multiple omics datasets, revealing new communities and functionally related groups in microbial strains, cell line gene expression patterns and fetal genomic variation. We also derived enrichment scores attributable to putatively meaningful biological factors in these datasets that can serve as hypothesis generators facilitating new sets of testable hypotheses. Availability and implementation omeClust is open-source software, and the implementation is available online at http://github.com/omicsEye/omeClust. Supplementary information Supplementary data are available at Bioinformatics online. 

Abstract Summary Heterogeneity is a hallmark of many complex human diseases, and unsupervised heterogeneity analysis has been extensively conducted using high-throughput molecular measurements and histopathological imaging features. ‘Classic’ heterogeneity analysis has been based on simple statistics such as mean, variance and correlation. Network-based analysis takes interconnections as well as individual variable properties into consideration and can be more informative. Several Gaussian graphical model (GGM)-based heterogeneity analysis techniques have been developed, but friendly and portable software is still lacking. To facilitate more extensive usage, we develop the R package HeteroGGM, which conducts GGM-based heterogeneity analysis using the advanced penaliztaion techniques, can provide informative summary and graphical presentation, and is efficient and friendly. Availabilityand implementation The package is available at https://CRAN.R-project.org/package=HeteroGGM. Supplementary information Supplementary data are available at Bioinformatics online. 

Abstract Summary Accurate prediction of drug–target interactions (DTI) is crucial for drug discovery. Recently, deep learning (DL) models for show promising performance for DTI prediction. However, these models can be difficult to use for both computer scientists entering the biomedical field and bioinformaticians with limited DL experience. We present DeepPurpose, a comprehensive and easy-to-use DL library for DTI prediction. DeepPurpose supports training of customized DTI prediction models by implementing 15 compound and protein encoders and over 50 neural architectures, along with providing many other useful features. We demonstrate state-of-the-art performance of DeepPurpose on several benchmark datasets. Availability and implementation https://github.com/kexinhuang12345/DeepPurpose. Supplementary information Supplementary data are available at Bioinformatics online.