MOTIVATION: Gene regulatory network (GRN) inference is a complex task aiming to unravel regulatory interactions between genes in a cell. A major shortcoming of most GRN inference methods is that they do not attempt to find the optimal sparsity, i.e. the single best GRN, which is important when applying GRN inference in a real situation. Instead, the sparsity tends to be controlled by an arbitrarily set hyperparameter. RESULTS: In this paper, two new methods for predicting the optimal sparsity of GRNs are formulated and benchmarked on simulated perturbation-based gene expression data using four GRN inference methods: LASSO, Zscore, LSCON, and GENIE3. Both sparsity prediction methods are defined using the hypothesis that the topology of real GRNs is scale-free, and are evaluated based on their ability to predict the sparsity of the true GRN. The results show that the new topology-based approaches reliably predict a sparsity close to the true one. This ability is valuable for real-world applications where a single GRN is inferred from real data. In such situations, it is vital to be able to infer a GRN with the correct sparsity. AVAILABILITY AND IMPLEMENTATION: https://bitbucket.org/sonnhammergrni/powerlaw_sparsity/ and https://codeocean.com/capsule/4393635/.

MOTIVATION: Inference of gene regulatory network (GRN) is challenging due to the inherent sparsity of the GRN matrix and noisy expression data, often leading to a high possibility of false positive or negative predictions. To address this, it is essential to leverage the sparsity of the GRN matrix and develop a robust method capable of handling varying levels of noise in the data. Moreover, most existing GRN inference methods produce only fixed point estimates, which lack the flexibility and informativeness for comprehensive network analysis. In contrast, a Bayesian approach that yields closed-form posterior distributions allows probabilistic link selection, offering insights into the statistical confidence of each possible link. Consequently, it is important to engineer a Bayesian GRN inference method and rigorously execute a benchmark evaluation compared to state-of-the-art methods. RESULTS: We propose a method-Bayesian inference of GRN via Sparse Modelling (BiGSM). BiGSM effectively exploits the sparsity of the GRN matrix and infers the posterior distributions of GRN links from noisy expression data by using the maximum likelihood based learning. We thoroughly benchmarked BiGSM using biological and simulated datasets including GeneNetWeaver, GeneSPIDER, and GRNbenchmark. The benchmark test evaluates its accuracy and robustness across varying noise levels and data models. Using point-estimate based performance measures, BiGSM provides an overall best performance in comparison with several state-of-the-art methods including GENIE3, LASSO, LSCON, and Zscore. Additionally, BiGSM is the only method in the set of competing methods that provides posteriors for the GRN weights, helping to decipher confidence across predictions. AVAILABILITY AND IMPLEMENTATION: Code implemented via MATLAB and Python are available at Github: https://github.com/SachLab/BiGSM and archived at zenodo.

BACKGROUND: Machine learning involves strategies and algorithms that may assist bioinformatics analyses in terms of data mining and knowledge discovery. In several applications, viz. in Life Sciences, it is often more important to understand how a prediction was obtained rather than knowing what prediction was made. To this end so-called interpretable machine learning has been recently advocated. In this study, we implemented an interpretable machine learning package based on the rough set theory. An important aim of our work was provision of statistical properties of the models and their components. RESULTS: We present the R.ROSETTA package, which is an R wrapper of ROSETTA framework. The original ROSETTA functions have been improved and adapted to the R programming environment. The package allows for building and analyzing non-linear interpretable machine learning models. R.ROSETTA gathers combinatorial statistics via rule-based modelling for accessible and transparent results, well-suited for adoption within the greater scientific community. The package also provides statistics and visualization tools that facilitate minimization of analysis bias and noise. The R.ROSETTA package is freely available at https://github.com/komorowskilab/R.ROSETTA . To illustrate the usage of the package, we applied it to a transcriptome dataset from an autism case-control study. Our tool provided hypotheses for potential co-predictive mechanisms among features that discerned phenotype classes. These co-predictors represented neurodevelopmental and autism-related genes. CONCLUSIONS: R.ROSETTA provides new insights for interpretable machine learning analyses and knowledge-based systems. We demonstrated that our package facilitated detection of dependencies for autism-related genes. Although the sample application of R.ROSETTA illustrates transcriptome data analysis, the package can be used to analyze any data organized in decision tables.

MOTIVATION: The search for causative genetic variants in rare diseases of presumed monogenic inheritance has been boosted by the implementation of whole exome (WES) and whole genome (WGS) sequencing. In many cases, WGS seems to be superior to WES, but the analysis and visualization of the vast amounts of data is demanding. RESULTS: To aid this challenge, we have developed a new tool-RareVariantVis-for analysis of genome sequence data (including non-coding regions) for both germ line and somatic variants. It visualizes variants along their respective chromosomes, providing information about exact chromosomal position, zygosity and frequency, with point-and-click information regarding dbSNP IDs, gene association and variant inheritance. Rare variants as well as de novo variants can be flagged in different colors. We show the performance of the RareVariantVis tool in the Genome in a Bottle WGS data set. AVAILABILITY AND IMPLEMENTATION: https://www.bioconductor.org/packages/3.3/bioc/html/RareVariantVis.html CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.