Background: Even though several computational methods for rhythmicity detection and analysis of biological data have been proposed in recent years, classical trigonometric regression based on cosinor still has several advantages over these methods and is still widely used. Different software packages for cosinor-based rhythmometry exist, but lack certain functionalities and require data in different, non-unified input formats.Results: We present CosinorPy, a Python implementation of cosinor-based methods for rhythmicity detection and analysis. CosinorPy merges and extends the functionalities of existing cosinor packages. It supports the analysis of rhythmic data using single- or multi-component cosinor models, automatic selection of the best model, population-mean cosinor regression, and differential rhythmicity assessment. Moreover, it implements functions that can be used in a design of experiments, a synthetic data generator, and import and export of data in different formats.Conclusion: CosinorPy is an easy-to-use Python package for straightforward detection and analysis of rhythmicity requiring minimal statistical knowledge, and produces publication-ready figures. Its code, examples, and documentation are available to download fromhttps://github.com/mmoskon/CosinorPy. CosinorPy can be installed manually or by using pip, the package manager for Python packages. The implementation reported in this paper corresponds to the software release v1.1.

Boolean descriptions of gene regulatory networks can provide an insight into interactions between genes. Boolean networks hold predictive power, are easy to understand, and can be used to simulate the observed networks in different scenarios.

Hepatocellular carcinoma (HCC) is a major health problem around the world. The management of this disease is complicated by the lack of noninvasive diagnostic tools and the few treatment options available. Better clinical outcomes can be achieved if HCC is detected early, but unfortunately, clinical signs appear when the disease is in its late stages. We aim to identify novel genes that can be targeted for the diagnosis and therapy of HCC. We performed a meta-analysis of transcriptomics data to identify differentially expressed genes and applied network analysis to identify hub genes. Fatty acid metabolism, complement and coagulation cascade, chemical carcinogenesis and retinol metabolism were identified as key pathways in HCC. Furthermore, we integrated transcriptomics data into a reference human genome-scale metabolic model to identify key reactions and subsystems relevant in HCC. We conclude that fatty acid activation, purine metabolism, vitamin D, and E metabolism are key processes in the development of HCC and therefore need to be further explored for the development of new therapies. We provide the first evidence that GABRP, HBG1 and DAK (TKFC) genes are important in HCC in humans and warrant further studies.

Quantitative modelling of biological systems has become an indispensable computational approach in the design of novel and analysis of existing biological systems. However, kinetic data that describe the system's dynamics need to be known in order to obtain relevant results with the conventional modelling techniques. These data are often hard or even impossible to obtain. Here, we present a quantitative fuzzy logic modelling approach that is able to cope with unknown kinetic data and thus produce relevant results even though kinetic data are incomplete or only vaguely defined. Moreover, the approach can be used in the combination with the existing state-of-the-art quantitative modelling techniques only in certain parts of the system, i.e., where kinetic data are missing. The case study of the approach proposed here is performed on the model of three-gene repressilator.

• Several challenges must be addressed when performing context-specific model extraction. • We propose a framework for efficient extraction/analysis of genome scale metabolic models. • We highlight the impact of choice of model extraction method (MEM) on the output models. • We highlight the impact of thresholding rules and values on the output models. • Cyp51 knockout mice diet experiment data are used as a case study.