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Biology subjects

Garbulowski, M.

Publications and source records attributed to Garbulowski, M..

3 recordsLinked to original sources

GeneSNAKE: a Python package for benchmarking and simulation of gene regulatory networks and perturbation-induced expression data

Understanding how genes interact with and regulate each other is a key challenge in systems biology. One of the primary methods to study this is through gene regulatory networks (GRNs). The field of GRN inference however faces many challenges, which necessitates effective tools for evaluating inference methods. For this purpose, data that corresponds to a known GRN, from various conditions and experimental setups is necessary, which is only possible to attain via simulation. Today, most existing tools for GRN-based simulation are limited either in network or data properties, with few or no options to modify these properties. To address these limitations we present GeneSNAKE, a Python package designed to allow users to generate biologically realistic GRNs, and expression data for benchmarking purposes. GeneSNAKE allows the user to control a wide range of network and data properties, including several distinct noise models. GeneSNAKE improves on previous work in the field by adding a perturbation model and a wide range of perturbation schemes along with the ability to control the noise and the perturbation strength. For benchmarking, GeneSNAKE offers a number of functions both for comparing network similarity, and properties in data and GRNs. These functions can further be used to study properties of biological data to produce simulated data with more realistic properties. GeneSNAKE is an open-source, comprehensive simulation and benchmarking package with powerful capabilities that are not combined in any other single package, and thanks to the Python implementation it can be extended and modified by users.

bioinformatics↗

Comprehensive analysis of the RBP regulome reveals functional modules and drug candidates in liver cancer

RNA binding proteins (RBPs) are essential components of the transcriptomic regulome. Identifying the RBP regulome in cancer cells is crucial to discovering and understanding carcinogenesis mechanisms and providing new therapeutic targets. Here, we aimed to reveal the regulome of liver cancer upon specific perturbations. To this end, we applied a consensus Gene Regulatory Network (GRN) approach using knockdown data for the liver cancer cell line HepG2. By incorporating multiple GRNs from diverse inference methods, we constructed a highly precise GRN. To validate our results, we comprehensively evaluated the consensus GRN, focusing on characterizing the most relevant aspects of the liver cancer regulome. This included utilizing eCLIP-seq and RAPseq data to verify RBP interactions and binding sites. In addition, we performed an enrichment analysis of network modules and drug repurposing based on the inferred GRN. Taken together, our findings demonstrate the critical roles of RBP regulatory interactions in liver cancer that can be employed to improve treatment strategies.

cancer biology↗

R.ROSETTA: a package for analysis of rule-based classification models

MotivationFor machine learning to matter beyond intellectual curiosity, the models developed therefrom must be adopted within the greater scientific community. In this study, we developed an interpretable machine learning framework that allows identification of semantics from various datatypes. Our package can analyze and illuminate co-predictive mechanisms reflecting biological processes. ResultsWe present R.ROSETTA, an R package for building and analyzing 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. Investigating case-control studies of autism, we showed that our tool provided hypotheses for potential interdependencies among features that discerned phenotype classes. These interdependencies regarded neurodevelopmental and autism-related genes. Although our sample application of R.ROSETTA was used for transcriptomic data analysis, R.ROSETTA works perfectly with any decision-related omics data. AvailabilityThe R.ROSETTA package is freely available at https://github.com/komorowskilab/R.ROSETTA. Contactmateusz.garbulowski@icm.uu.se (Mateusz Garbulowski), jan.komorowski@icm.uu.se (Jan Komorowski)

bioinformatics↗