Phenomics and Robust Multiomics Data for Cardiovascular Disease Subtyping.

The complex landscape of cardiovascular diseases encompasses a wide range of related pathologies arising from diverse molecular mechanisms and exhibiting heterogeneous phenotypes. This variety of manifestations poses significant challenges in the development of treatment strategies. The increasing availability of precise phenotypic and multiomics data of cardiovascular disease patient populations has spurred the development of a variety of computational disease subtyping techniques to identify distinct subgroups with unique underlying pathogeneses. In this review, we outline the essential components of computational approaches to select, integrate, and cluster omics and clinical data in the context of cardiovascular disease research. We delve into the challenges faced during different stages of the analysis, including feature selection and extraction, data integration, and clustering algorithms. Next, we highlight representative applications of subtyping pipelines in heart failure and coronary artery disease. Finally, we discuss the current challenges and future directions in the development of robust subtyping approaches that can be implemented in clinical workflows, ultimately contributing to the ongoing evolution of precision medicine in health care.

Converging on a Cure: The Roads to Predictive Immunotherapy.

SUMMARY: Convergence science teams integrating clinical, biological, engineering, and computational expertise are inventing new forecast systems to monitor and predict evolutionary changes in tumor and immune interactions during early cancer progression and therapeutic response. The resulting methods should inform a new predictive medicine paradigm to select adaptive immunotherapeutic regimens personalized to patients' tumors at a given time during their cancer progression for durable patient response.

Emerging Personalized Opportunities for Enhancing Translational Readthrough in Rare Genetic Diseases and Beyond.

Nonsense mutations trigger premature translation termination and often give rise to prevalent and rare genetic diseases. Consequently, the pharmacological suppression of an unscheduled stop codon represents an attractive treatment option and is of high clinical relevance. At the molecular level, the ability of the ribosome to continue translation past a stop codon is designated stop codon readthrough (SCR). SCR of disease-causing premature termination codons (PTCs) is minimal but small molecule interventions, such as treatment with aminoglycoside antibiotics, can enhance its frequency. In this review, we summarize the current understanding of translation termination (both at PTCs and at cognate stop codons) and highlight recently discovered pathways that influence its fidelity. We describe the mechanisms involved in the recognition and readthrough of PTCs and report on SCR-inducing compounds currently explored in preclinical research and clinical trials. We conclude by reviewing the ongoing attempts of personalized nonsense suppression therapy in different disease contexts, including the genetic skin condition epidermolysis bullosa.

Emerging technologies in personalized medicine.

A variety of technologies are emerging to help clinicians provide patient-specific diagnosis and therapies. This special edition of the Molecular Aspects of Medicine is a collection of mini reviews covering a broad range of topics, from systems to model patient variants and discover therapies (Microphysiological systems with patient derived tissue and CRISPR-humanized animal models), to new modalities in diagnostics and therapeutics (Extracellular Vesicles, RNA therapeutics, microbiome and molecular dynamics).

Estado actual y retos futuros en el tratamiento de las enfermedades reumáticas / Current status and future challenges in the treatment of rheumatic diseases

Las nuevas estrategias, que incluyen el diagnóstico y el tratamiento tempranos, el enfoque de tratamiento dirigido a un objetivo, la remisión como ese objetivo principal del tratamiento, la participación de los pacientes en las decisiones terapéuticas, junto con el desarrollo de nuevos tratamientos efectivos, han cambiado las expectativas de los reumatólogos y de los pacientes con enfermedades reumáticas. Todavía existen, sin embargo, importantes desafíos tales como la seguridad a largo plazo de los tratamientos actuales y poder escoger tratamientos más individualizados y eficaces, de forma tal de elegir el mejor tratamiento para cada paciente. El futuro, como en el resto de la medicina, probablemente sea la prevención del desarrollo de enfermedades reumáticas. Discutiremos estos temas en esta revisión. (AU)

New strategies, including early diagnosis and treatment, targeted therapy, remission as the main objective of treatment, patient involvement in therapeutic decision-making, and the development of new effective therapies, have changed the expectations of rheumatologists and patients with rheumatic diseases.There are still serious challenges, such as the long-term safety of current treatments and the ability to make more individualized and effective treatments to choose the best treatment for each patient. The future, as that of the whole of medical science, will probably lie in preventing the development of rheumatic diseases. We will discuss these issues in this review. (AU)

CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia.

INTRODUCTION: Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? AREAS COVERED: The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. EXPERT OPINION: CYP2D6 genotype can influence opioids' pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.

Laying the groundwork for the Biobank of Rare Malignant Neoplasms at the service of the Hellenic Network of Precision Medicine on Cancer.

Biobanks constitute an integral part of precision medicine. They provide a repository of biospecimens that may be used to elucidate the pathophysiology, support diagnoses, and guide the treatment of diseases. The pilot biobank of rare malignant neoplasms has been established in the context of the Hellenic Network of Precision Medicine on Cancer and aims to enhance future clinical and/or research studies in Greece by collecting, processing, and storing rare malignant neoplasm samples with associated data. The biobank currently comprises 553 samples; 384 samples of hematopoietic and lymphoid tissue malignancies, 72 samples of pediatric brain tumors and 97 samples of malignant skin neoplasms. In this article, sample collections and their individual significance in clinical research are described in detail along with computational methods developed specifically for this project. A concise review of the Greek biobanking landscape is also delineated, in addition to recommended technologies, methodologies and protocols that were integrated during the creation of the biobank. This project is expected to re­enforce current clinical and research studies, introduce advances in clinical and genetic research and potentially aid in future targeted drug discovery. It is our belief that the future of medical research is entwined with accessible, effective, and ethical biobanking and that our project will facilitate research planning in the '­omic' era by contributing high­quality samples along with their associated data.

How Single-Cell Technologies Have Provided New Insights Into Atherosclerosis.

The development of innovative single-cell technologies has allowed the high-dimensional transcriptomic and proteomic profiling of individual blood and tissue cells. Recent single-cell studies revealed a new cellular heterogeneity of atherosclerotic plaque tissue and allowed a better understanding of distinct immune functional states in the context of atherosclerosis. In this brief review, we describe how single-cell technologies have shed a new light on the cellular composition of atherosclerotic plaques, and their response to diet perturbations or genetic manipulation in mouse models of atherosclerosis. We discuss how single-cell RNA sequencing, cellular indexing of transcriptomes and epitopes by sequencing, transposase-accessible chromatin with high-throughput sequencing, and cytometry by time-of-flight platforms have empowered the identification of discrete immune, endothelial, and smooth muscle cell alterations in atherosclerosis progression and regression. Finally, we review how single-cell approaches have allowed mapping the cellular and molecular composition of human atherosclerotic plaques and the discovery of new immune alterations in plaques from patients with stroke.

[Moving towards a personalized oncology: The contribution of genomic techniques and artificial intelligence in the use of circulating tumor biomarkers]. / En marche vers une oncologie personnalisée : l'apport des techniques génomiques et de l'intelligence artificielle dans l'usage des biomarqueurs tumoraux circulants.

Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed.