Band 22, Heft 1 - Special Issue: 20 Years Journal of Integrative Bioinformatics; Guest Editor: Ralf Hofestädt

The Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben is a leading international plant science institute specializing in biodiversity and crop plant performance research. Over the last decade, all phases of the research data lifecycle were implemented as a continuous process in conjunction with information technology, standardization, and sustainable research data management (RDM) processes. Under the leadership of a team of data stewards, a research data infrastructure, process landscape, capacity building, and governance structures were successfully established. As a result, a generic research data infrastructure was created to serve the principles of good scientific practice, archiving research data in an accessible and sustainable manner, even before the FAIR criteria were formulated. In this paper, we discuss success stories as well as pitfalls and summarize the experiences from 15 years of operating a central RDM infrastructure. We present measures for agile requirements engineering, technical and organizational implementation, governance, training, and roll-out. We show the benefits of a participatory approach across all departments, personnel roles, and researcher profiles through pilot working groups and data management champions. As a result, an ambidextrous approach to data management was implemented, referring to the ability to efficiently combine operational needs, support daily tasks in compliance with the FAIR criteria, while remaining open to adopting technical innovations in an agile manner.

Although multiple aspects of molecular pathology underlying cardiovascular diseases (CVDs) have been revealed, the complete picture has yet to be elucidated. In this respect, annotation of the novel links between genes and atherosclerosis is of great importance for cardiovascular medicine. Aligning with our previous research, we aimed to analyze the cardiovascular predisposition contribution of the genes encoding Hero-proteins, polypeptides with chaperone activity. Following bioinformatic sources were utilized to annotate data regarding the cardiovascular contribution of Hero-proteins and their genes: SNPinfo Web Server, The Cardiovascular Disease Knowledge Portal, GTEx Portal, HaploReg, rSNPBase, RegulomeDB, atSNP, Gene Ontology, QTLbase, and the Blood eQTL browser. Almost all analyzed genes were characterized by a very high regulatory potential of tag SNPs (except BEX3 ). Multiple substantial impacts of the analyzed SNPs on histone modifications, eQTL effects on CVD-related genes, and binding to transcription factors involved in biological processes pathogenetically significant for CVDs have been discovered. Here we provide in silico evidence of the involvement of genes C9orf16 (BBLN) , C11orf58 , SERBP1 , SERF2 , and C19orf53 in CVDs and their risk factors (high blood pressure, dyslipidemia, obesity, arrhythmias, etc.), thus revealing Hero-proteins as putative actors in the pathobiology of the heart and vessels.

Sustainable software development requires the software to remain accessible and maintainable over long time. This is particularly challenging in a scientific context. For example, fewer than one third of tools and platforms for biological network representation, analysis, and visualisation have been available and supported over a period of 15 years. One of those tools is Vanted, which has been developed and actively supported over the past 20 years. In this work, we discuss sustainable software development in science and investigate which software tools for biological network representation, analysis, and visualisation are maintained over a period of at least 15 years. With Vanted as a case study, we highlight five key insights that we consider crucial for sustainable, long-term software development and software maintenance in science.

Stem cells are capable of self-renewal and differentiation into various cell types, showing significant potential for cellular therapies and regenerative medicine, particularly in cardiovascular diseases. The differentiation to cardiomyocytes replicates the embryonic heart development, potentially supporting cardiac regeneration. Cardiomyogenesis is controlled by complex post-transcriptional regulation that affects the construction of gene regulatory networks (GRNs), such as: alternative polyadenylation (APA), length changes in untranslated regulatory regions (3′UTRs), and microRNA (miRNA) regulation. To deepen our understanding of the cardiomyogenesis process, we have modeled a GRN for each day of cardiomyocyte differentiation. Then, each GRN was automatically transformed by four transformation rules to a Petri net and simulated using the software VANESA. The Petri nets highlighted the relationship between genes and alternative isoforms, emphasizing the inhibition of miRNA on APA isoforms with varying 3′UTR lengths. Moreover, in silico simulation of miRNA knockout enabled the visualization of the consequential effects on isoform expression. Our Petri net models provide a resourceful tool and holistic perspective to investigate the functional orchestra of transcript regulation that differentiate hESCs to cardiomyocytes. Additionally, the models can be adapted to investigate post-transcriptional GRN in other biological contexts.

The glycoproteins 41 (gp41) of human immunodeficiency virus (HIV), located on the virus’s external surface, form six-helix bundles that facilitate viral entry into the host cell. Theta defensins, cyclic peptides, inhibit the formation of these bundles by binding to the GP41 CHR region. RC101, a synthetic analog of theta-defensin molecules, exhibits activity against various HIV subtypes. Molecular docking of the CHR and RC101 was done using MDockPeP and Hawdock server. The type of bonds and the essential amino acids in binding were identified using AlphaFold3, CHIMERA, RING, and CYTOSCAPE. Mutable amino acids within the peptide were determined using the CUPSAT and Duet. Thirty-two new peptides were designed, and their interaction with the CHR of the gp41 was analyzed. The physicochemical properties, toxicity, allergenicity, and antigenicity of peptides were also investigated. Most of the designed peptides exhibited higher binding affinities to the target compared to RC101; notably, peptides 1 and 4 had the highest binding affinity and demonstrated a greater percentage of interactions with critical amino acids of CHR. Peptides A and E displayed the best physiochemical properties among designed peptides. The designed peptides may present a new generation of anti-HIV drugs, which may reduce the likelihood of drug resistance.