MOTIVATION: The rapid increase of bio-medical literature makes it harder and harder for scientists to keep pace with the discoveries on which they build their studies. Therefore, computational tools have become more widespread, among which network analysis plays a crucial role in several life-science contexts. Nevertheless, building correct and complete networks about some user-defined biomedical topics on top of the available literature is still challenging. RESULTS: We introduce NetMe 2.0, a web-based platform that automatically extracts relevant biomedical entities and their relations from a set of input texts-i.e. in the form of full-text or abstract of PubMed Central's papers, free texts, or PDFs uploaded by users-and models them as a BioMedical Knowledge Graph (BKG). NetMe 2.0 also implements an innovative Retrieval Augmented Generation module (Graph-RAG) that works on top of the relationships modeled by the BKG and allows the distilling of well-formed sentences that explain their content. The experimental results show that NetMe 2.0 can infer comprehensive and reliable biological networks with significant Precision-Recall metrics when compared to state-of-the-art approaches. AVAILABILITY AND IMPLEMENTATION: https://netme.click/.

In this paper, we present MASFENON, a novel multi-agent network interactions simulation algorithm that allows us to consider the dynamics within and between each agent and its associated network. MASFENON can be applied in various domains. Here, we will focus on an application related to epidemics network modeling. By combining propagation, dissipation, and conservation principles with some principles inspired by chaos theory, MASFENON offers a novel approach to model infectious disease spread across communities.

SUMMARY: The discovery of differential gene-gene correlations across phenotypical groups can help identify the activation/deactivation of critical biological processes underlying specific conditions. The presented R package, provided with a count and design matrix, extract networks of group-specific interactions that can be interactively explored through a shiny user-friendly interface. For each gene-gene link, differential statistical significance is provided through robust linear regression with an interaction term. AVAILABILITY AND IMPLEMENTATION: DEGGs is implemented in R and available on GitHub at https://github.com/elisabettasciacca/DEGGs. The package is also under submission on Bioconductor.

MOTIVATION: The study of the Human Virome remains challenging nowadays. Viral metagenomics, through high-throughput sequencing data, is the best choice for virus discovery. The metagenomics approach is culture-independent and sequence-independent, helping search for either known or novel viruses. Though it is estimated that more than 40% of the viruses found in metagenomics analysis are not recognizable, we decided to analyze several tools to identify and discover viruses in RNA-seq samples. RESULTS: We have analyzed eight Virus Tools for the identification of viruses in RNA-seq data. These tools were compared using a synthetic dataset of 30 viruses and a real one. Our analysis shows that no tool succeeds in recognizing all the viruses in the datasets. So we can conclude that each of these tools has pros and cons, and their choice depends on the application domain. AVAILABILITY: Synthetic data used through the review and raw results of their analysis can be found at https://zenodo.org/record/6426147. FASTQ files of real data can be found in GEO (https://www.ncbi.nlm.nih.gov/gds) or ENA (https://www.ebi.ac.uk/ena/browser/home). Raw results of their analysis can be downloaded from https://zenodo.org/record/6425917.

BACKGROUND: RNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this technology produces a vast amount of data requiring sophisticated computational approaches for their analysis than other traditional technologies such as Real-Time PCR or microarrays, strongly discouraging non-expert users. For this reason, dozens of pipelines have been deployed for the analysis of RNA-Seq data. Although interesting, these present several limitations and their usage require a technical background, which may be uncommon in small research laboratories. Therefore, the application of these technologies in such contexts is still limited and causes a clear bottleneck in knowledge advancement. RESULTS: Motivated by these considerations, we have developed RNAdetector, a new free cross-platform and user-friendly RNA-Seq data analysis software that can be used locally or in cloud environments through an easy-to-use Graphical User Interface allowing the analysis of coding and non-coding RNAs from RNA-Seq datasets of any sequenced biological species. CONCLUSIONS: RNAdetector is a new software that fills an essential gap between the needs of biomedical and research labs to process RNA-Seq data and their common lack of technical background in performing such analysis, which usually relies on outsourcing such steps to third party bioinformatics facilities or using expensive commercial software.

Despite the unprecedented growth in our understanding of cell biology, it still remains challenging to connect it to experimental data obtained with cells and tissues' physiopathological status under precise circumstances. This knowledge gap often results in difficulties in designing validation experiments, which are usually labor-intensive, expensive to perform, and hard to interpret. Here we propose PHENSIM, a computational tool using a systems biology approach to simulate how cell phenotypes are affected by the activation/inhibition of one or multiple biomolecules, and it does so by exploiting signaling pathways. Our tool's applications include predicting the outcome of drug administration, knockdown experiments, gene transduction, and exposure to exosomal cargo. Importantly, PHENSIM enables the user to make inferences on well-defined cell lines and includes pathway maps from three different model organisms. To assess our approach's reliability, we built a benchmark from transcriptomics data gathered from NCBI GEO and performed four case studies on known biological experiments. Our results show high prediction accuracy, thus highlighting the capabilities of this methodology. PHENSIM standalone Java application is available at https://github.com/alaimos/phensim, along with all data and source codes for benchmarking. A web-based user interface is accessible at https://phensim.tech/.

Next-Generation Sequencing (NGS) is a high-throughput technology widely applied to genome sequencing and transcriptome profiling. RNA-Seq uses NGS to reveal RNA identities and quantities in a given sample. However, it produces a huge amount of raw data that need to be preprocessed with fast and effective computational methods. RNA-Seq can look at different populations of RNAs, including ncRNAs. Indeed, in the last few years, several ncRNAs pipelines have been developed for ncRNAs analysis from RNA-Seq experiments. In this paper, we analyze eight recent pipelines (iSmaRT, iSRAP, miARma-Seq, Oasis 2, SPORTS1.0, sRNAnalyzer, sRNApipe, sRNA workbench) which allows the analysis not only of single specific classes of ncRNAs but also of more than one ncRNA classes. Our systematic performance evaluation aims at guiding users to select the appropriate pipeline for processing each ncRNA class, focusing on three key points: (i) accuracy in ncRNAs identification, (ii) accuracy in read count estimation and (iii) deployment and ease of use.

BACKGROUND: Several large public repositories of microarray datasets and RNA-seq data are available. Two prominent examples include ArrayExpress and NCBI GEO. Unfortunately, there is no easy way to import and manipulate data from such resources, because the data is stored in large files, requiring large bandwidth to download and special purpose data manipulation tools to extract subsets relevant for the specific analysis. RESULTS: TACITuS is a web-based system that supports rapid query access to high-throughput microarray and NGS repositories. The system is equipped with modules capable of managing large files, storing them in a cloud environment and extracting subsets of data in an easy and efficient way. The system also supports the ability to import data into Galaxy for further analysis. CONCLUSIONS: TACITuS automates most of the pre-processing needed to analyze high-throughput microarray and NGS data from large publicly-available repositories. The system implements several modules to manage large files in an easy and efficient way. Furthermore, it is capable deal with Galaxy environment allowing users to analyze data through a user-friendly interface.

Posttranscriptional cross talk and communication between genes mediated by microRNA response element (MREs) yield large regulatory competing endogenous RNA (ceRNA) networks. Their inference may improve the understanding of pathologies and shed new light on biological mechanisms. A variety of RNA: messenger RNA, transcribed pseudogenes, noncoding RNA, circular RNA and proteins related to RNA-induced silencing complex complex interacting with RNA transfer and ribosomal RNA have been experimentally proved to be ceRNAs. We retrace the ceRNA hypothesis of posttranscriptional regulation from its original formulation [Salmena L, Poliseno L, Tay Y, et al. Cell 2011;146:353-8] to the most recent experimental and computational validations. We experimentally analyze the methods in literature [Li J-H, Liu S, Zhou H, et al. Nucleic Acids Res 2013;42:D92-7; Sumazin P, Yang X, Chiu H-S, et al. Cell 2011;147:370-81; Sarver AL, Subramanian S. Bioinformation 2012;8:731-3] comparing them with a general machine learning approach, called ceRNA predIction Algorithm, evaluating the performance in predicting novel MRE-based ceRNAs.

MOTIVATION: The identification of drug-target interaction (DTI) represents a costly and time-consuming step in drug discovery and design. Computational methods capable of predicting reliable DTI play an important role in the field. Recently, recommendation methods relying on network-based inference (NBI) have been proposed. However, such approaches implement naive topology-based inference and do not take into account important features within the drug-target domain. RESULTS: In this article, we present a new NBI method, called domain tuned-hybrid (DT-Hybrid), which extends a well-established recommendation technique by domain-based knowledge including drug and target similarity. DT-Hybrid has been extensively tested using the last version of an experimentally validated DTI database obtained from DrugBank. Comparison with other recently proposed NBI methods clearly shows that DT-Hybrid is capable of predicting more reliable DTIs. AVAILABILITY: DT-Hybrid has been developed in R and it is available, along with all the results on the predictions, through an R package at the following URL: http://sites.google.com/site/ehybridalgo/.