ПРИНЦИПИ МАТЕМАТИЧНОГО МОДЕЛЮВАННЯ мікроРНК-ОПОСЕРЕДКОВАНИХ СИГНАЛЬНИХ МЕРЕЖ ПРИ ЗАХВОРЮВАННЯХ ЛЮДИНИ

Background. Taking into account the growth of scientific knowledge and the discovery of new miRNAs and their gene targets, approaches to computational modeling of new functional associations between differentiated expression of miRNAs and diseases, as well as phenotypic patterns of miRNAs expression in gene regulatory networks. The goal of the conceptualization was the results of comparatively recent studies in systems biology, which use various kinetic modeling methods to help identify possibilities regarding the regulatory function and therapeutic potential of miRNAs in human diseases. Materials and methods. Results. Some of the key computational aspects of mathematical modeling are also considered, which include: regulation of miRNAs-mediated network motifs in the regulation of gene expression; models of miRNAs biogenesis and miRNA target interactions; inclusion of such models in complex pathways of disease development, systemic understanding of their pathophysiological context. It is concluded that the efficiency and practicality of using small miRNA-associated network motifs, simplified to several components, to study the prognostic characteristics of the simulated network dynamics in diseases and physiological conditions. It is emphasized that most experimental studies focus on direct interactions of target miRNAs. Thus, the role of miRNAs in systems is revealed and, therefore, a systematic understanding of gene-mediated miRNA gene repression is provided. Conclusions. However, in addition to the usual interactions of target miRNAs, recent experiments have shown that primary miRNAs or miRNA precursors formed during miRNA biogenesis can also compete with mature miRNAs for binding sites on target miRNAs. It is also important to move from the temporal dynamics of gene regulation by miRNAs, to the analysis and modeling of miRNA spatial information in cells as different subcellular locations.Розглянуто підходи до обчислювального моделювання нових функціональних асоціацій між диференційованою експресією miRNAs і захворюваннями, а також фенотипових патернів експресії miRNAs у генних регуляторних мережах. Метою концептуалізації стали результати порівняно недавніх досліджень системної біології, в яких використано різні методи кінетичного моделювання, що допомагають виявити можливості стосовно регуляторної функції і терапевтичного потенціалу miRNAs при захворюваннях людини. Розглянуто також деякі з ключових обчислювальних аспектів математичного моделювання, що включають: регуляції опосередкованих miRNAs мережевих мотивів у регуляції експресії генів, моделі біогенезу miRNAs і взаємодії miRNA-мішеней, включення таких моделей у складні шляхи розвитку захворювань, системного розуміння їх патофізіологічного контексту. Зроблено висновок про ефективність і практичність використання невеликих miRNA-асоційованих мережевих мотивів, спрощених до декількох компонентів, для вивчення прогностичних характеристик модельованої мережевої динаміки при захворюваннях і фізіологічних станах. Підкреслюється, що більшість експериментальних досліджень зосереджуються на прямих взаємодіях miRNA-мішеней. Отже, розкривається роль мікроРНК у системах, забезпечуючи системне розуміння опосередкованої мікроРНК репресії генів. однак, окрім звичайних взаємодій miRNA-мішеней, нещодавні експерименти показали, що первинні miRNA або попередники miRNA, що утворюються під час біогенезу miRNA, також можуть конкурувати зі зрілими miRNA за місця зв'язування на цільових miRNA. Також важливо перейти від тимчасової динаміки регуляції генів за допомогою miRNAs, до аналізу та моделювання просторової інформації miRNA в клітинах, як різних субклітинних розташуваннях

The intricate interplay between epigenetic events, alternative splicing and noncoding RNA deregulation in colorectal cancer

Colorectal cancer (CRC) results from a transformation of colonic epithelial cells into adenocarcinoma cells due to genetic and epigenetic instabilities, alongside remodelling of the surrounding stromal tumour microenvironment. Epithelial-specific epigenetic variations escorting this process include chromatin remodelling, histone modifications and aberrant DNA methylation, which influence gene expression, alternative splicing and function of non-coding RNA. In this review, we first highlight epigenetic modulators, modifiers and mediators in CRC, then we elaborate on causes and consequences of epigenetic alterations in CRC pathogenesis alongside an appraisal of the complex feedback mechanisms realized through alternative splicing and non-coding RNA regulation. An emphasis in our review is put on how this intricate network of epigenetic and post-transcriptional gene regulation evolves during the initiation, progression and metastasis formation in CRC

White Paper 2: Origins, (Co)Evolution, Diversity & Synthesis Of Life

Publicado en Madrid, 185 p. ; 17 cm.How life appeared on Earth and how then it diversified into the different and currently existing forms of life are the unanswered questions that will be discussed this volume. These questions delve into the deep past of our planet, where biology intermingles with geology and chemistry, to explore the origin of life and understand its evolution, since “nothing makes sense in biology except in the light of evolution” (Dobzhansky, 1964). The eight challenges that compose this volume summarize our current knowledge and future research directions touching different aspects of the study of evolution, which can be considered a fundamental discipline of Life Science. The volume discusses recent theories on how the first molecules arouse, became organized and acquired their structure, enabling the first forms of life. It also attempts to explain how this life has changed over time, giving rise, from very similar molecular bases, to an immense biological diversity, and to understand what is the hylogenetic relationship among all the different life forms. The volume further analyzes human evolution, its relationship with the environment and its implications on human health and society. Closing the circle, the volume discusses the possibility of designing new biological machines, thus creating a cell prototype from its components and whether this knowledge can be applied to improve our ecosystem. With an effective coordination among its three main areas of knowledge, the CSIC can become an international benchmark for research in this field

GEORAC: an RNA-seq Atlas Constructor for the Gene Expression Omnibus

The meteoric rise of next-generation sequencing technologies over the past 15 years has resulted in a voluminous amount of data generated by modern biological and clinical studies. RNA sequencing, colloquially referred to as RNA-Seq, is a next-generation approach capable of surveying and quantifying whole organism transcriptomes. RNA-Seq methods are valued over microarray assays for their ability to avoid cross-hybridization signal noise, to quantify gene or transcript expression without assay-specific upper limits, to natively provide single-nucleotide genomic resolution, and to allow for de novo transcriptome assemblies. Many thousands of RNA-Seq studies have been published over the past seven years, and a significant area of bioinformatics research has focused on the creation of atlases that aggregate RNA-Seq results. These atlases are crucially useful for surveying trends in gene expression across published studies, for inspecting potentially contentious claims made by novel or prior work, and for synthesizing future research directions. The Expression Atlas currently serves as the canonical example for an RNA-Seq atlas and presents results from over 3,000 studies across numerous model research organisms. An issue with the Expression Atlas is that it forcibly applies a uniform secondary re-analysis pipeline to each RNA-Seq study incorporated within its database; this approach presents a conceptual challenge to studies whose results have been generated and published using established, well-tested workflows. Thus, there exists a critical need to provide for construction of RNA-Seq atlases that precisely reflect original results presented within the literature, and the primary objective of this dissertation is to provide a workflow that allows for transparent, reproducible construction of RNA-Seq atlases from study meta- and expression data housed within the National Center for Biomedical Information’s Gene Expression Omnibus (GEO). The challenge of this goal is exacerbated by the highly flexible design of GEO, which allows researchers to define novel metadata attributes and values at will and to submit expression results in virtually any format. Following an introductory background into modern genomics and RNA-Seq, the second chapter of this work presents GEOMP, a metadata parser and relational database constructor for the Gene Expression Omnibus. The subsequent third chapter describes GEOMP2, an in-place augmentation of GEOMP that provides further atomization and loading of sample-specific characteristics tags; this chapter significantly presents results from a pilot study surveying bioinformatics methods reproducibility across the zebrafish, mouse, and human research communities using metadata parsed and output by GEOMP2. Chapter four details GEORGET, a pipeline designed to rehabilitate, translate, and load expression data pulled from GEO into the relational database store constructed by GEOMP2. Chapter five concludes with discussion of future directions needed to expand and improve upon the current GEORAC workflow and the associated methods reproducibility study

White Paper 4: Challenges In Biomedicine & Health

Publicado en Madrid, 231 p. ; 17 cm.A lesson that we have learned from the pandemia caused by coronavirus is that solutions in health require coordinated actions. Beside this and other emerging and re-emerging infectious diseases, millions of Europeans are suffering a plethora of disorders that are currently acquiring epidemic dimensions, including cancer, rare diseases, pain and food allergies, among others. New tools for prevention, diagnosis and treatment need to be urgently designed and implemented using new holistic and multidisciplinary approaches at three different levels (basic research, translational/clinical and public/social levels) and involving researchers, clinicians, industry and all stakeholders in the health system. The CSIC is excellently positioned to lead and coordinate these challenges in Biomedicine and Health.Peer reviewe

The Role of Non-Coding RNAs in the Human Placenta

Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the placenta they have been investigated very marginally. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, including placenta, are members of the group of microRNAs (miRNAs). Due to their quantity, it can be expected that the fairly larger group of other ncRNAs exerts far stronger effects than miRNAs. The syncytiotrophoblast of fetal origin forms the interface between fetus and mother, and releases permanently extracellular vesicles (EVs) into the maternal circulation which contain fetal proteins and RNA, including ncRNA, for communication with neighboring and distant maternal cells. Disorders of ncRNA in placental tissue, especially in trophoblast cells, and in EVs seem to be involved in pregnancy disorders, potentially as a cause or consequence. This review summarizes the current knowledge on placental ncRNA, their transport in EVs, and their involvement and pregnancy pathologies, as well as their potential for novel diagnostic tools

An Introduction to Programming for Bioscientists: A Python-based Primer

Computing has revolutionized the biological sciences over the past several decades, such that virtually all contemporary research in the biosciences utilizes computer programs. The computational advances have come on many fronts, spurred by fundamental developments in hardware, software, and algorithms. These advances have influenced, and even engendered, a phenomenal array of bioscience fields, including molecular evolution and bioinformatics; genome-, proteome-, transcriptome- and metabolome-wide experimental studies; structural genomics; and atomistic simulations of cellular-scale molecular assemblies as large as ribosomes and intact viruses. In short, much of post-genomic biology is increasingly becoming a form of computational biology. The ability to design and write computer programs is among the most indispensable skills that a modern researcher can cultivate. Python has become a popular programming language in the biosciences, largely because (i) its straightforward semantics and clean syntax make it a readily accessible first language; (ii) it is expressive and well-suited to object-oriented programming, as well as other modern paradigms; and (iii) the many available libraries and third-party toolkits extend the functionality of the core language into virtually every biological domain (sequence and structure analyses, phylogenomics, workflow management systems, etc.). This primer offers a basic introduction to coding, via Python, and it includes concrete examples and exercises to illustrate the language's usage and capabilities; the main text culminates with a final project in structural bioinformatics. A suite of Supplemental Chapters is also provided. Starting with basic concepts, such as that of a 'variable', the Chapters methodically advance the reader to the point of writing a graphical user interface to compute the Hamming distance between two DNA sequences.Comment: 65 pages total, including 45 pages text, 3 figures, 4 tables, numerous exercises, and 19 pages of Supporting Information; currently in press at PLOS Computational Biolog

Planetary health: an interdisciplinary perspective

This paper addresses the issue of planetary health under a multidisciplinary profile. It starts with defining the scope of planetary health, retracing its most salient historical points. It then reflects on the socio-political changes needed to achieve transformational change in society. The concepts of health literacy and environmental health literacy are explored as a useful means of disseminating and raising awareness about planetary health. Finally, a case study related to heart disease is explored to demonstrate why this approach is more necessary today than ever

A Novel Approach to Using Personal Response Systems and Diagrams to Foster Student Engagement in Large Lecture: Case Study of Instruction for Model-Based Reasoning in Biology

At UMass Amherst a method of personal response system (clickers) use in large lecture biology called Guided Application of Model-based Reasoning (GAMBR) has been designed to give students experiences in reasoning like expert biologists: In large lecture biology many instructors appear to use clickers mainly as a quizzing and attendance tool. Less well documented and examined are uses of clickers to facilitate cognitive engagement in learning scientific models and skills. In GAMBR, clicker questions ask students to apply and perturb biological models; this is designed to engage them in model-based reasoning. In an attempt to understand such a course, an exploratory case study of GAMBR was conducted to examine and describe three main components: clicker questions design, the hierarchical organization of the course, and student utterances during class-wide discussions. Field notes and course materials served as the primary basis for case study descriptions of hierarchical organization, clicker questions, and for open coding to generate new categories of student talk. A taxonomy of types of student utterances was identified, including utterances that suggested student engagement with the models. An important subset of the latter type suggested model-based reasoning. Results indicated that 89% of utterances during class-wide discussions following clicker questions suggested engagement with the model, and within those 33% suggested reasoning with the model. Two major types of diagrams were used with clicker questions. Model representation diagrams presented a partial model. Data diagrams presented data related to the model. Other questions had no accompanying diagram. Student talk that suggested engagement in model-based reasoning occurred at a higher frequency when clicker questions were accompanied by a diagram and especially with a model-representation diagram. A hypothesized model of six nested levels of processes in the instructional approach and hypotheses on why GAMBR produced a high percentage of model talk and model-based reasoning talk were generated, grounded in the case study observations of clicker question and course structure. It is suggested that GAMBR contains interesting alternatives to the more commonly used approach of peer instruction in large lecture biology courses using clickers, especially for those interested in promoting scientific reasoning