Single-Cell Analysis: from Innovative Omics to Target Therapy

Copyright: © 2012 Mannello F. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. To date, most of cell biology studies were performed on cell clusters, considering that all cells belonging to a peculiar cell type were identical. The renewed interest in cell-to-cell variation and its characterization enriched the concept of cellular heterogeneity, so far use, especially referred to cancer phenotypization [1]

Representing and querying disease networks using graph databases

BACKGROUND: Systems biology experiments generate large volumes of data of multiple modalities and this information presents a challenge for integration due to a mix of complexity together with rich semantics. Here, we describe how graph databases provide a powerful framework for storage, querying and envisioning of biological data. RESULTS: We show how graph databases are well suited for the representation of biological information, which is typically highly connected, semi-structured and unpredictable. We outline an application case that uses the Neo4j graph database for building and querying a prototype network to provide biological context to asthma related genes. CONCLUSIONS: Our study suggests that graph databases provide a flexible solution for the integration of multiple types of biological data and facilitate exploratory data mining to support hypothesis generation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13040-016-0102-8) contains supplementary material, which is available to authorized users

Medycyna nowej generacji

Praca recenzowana / peer-reviewed paperW ostatnim dziesięcioleciu, po rozszyfrowaniu ludzkiego genomu, nastąpił ogromny rozwój metod i technologii diagnostycznych zajmujących się wykrywaniem nowych biomarkerów i badaniem molekularnych mechanizmów powstawania chorób oraz działania leków. Te innowacyjne technologie i terapie niosą nadzieję na zmniejszenie rozpowszechnienia oraz poprawę wyników leczenia chorób, także tych dotychczas uważanych za nieuleczalne. Rozwój badań nad nowymi lekami z wykorzystaniem modelowania komputerowego oraz przenoszenie wyników wprost z laboratoriów do łóżka chorego w ramach medycyny translacyjnej pozwala na coraz szersze stosowanie nowych terapii molekularnie ukierunkowanych – dostosowanych do potrzeb każdego chorego. Obecnie celem medycyny jest jej personalizacja, czyli odpowiednia diagnostyka i terapia we właściwym czasie.In the last decade, after the deciphering of the human genome, a tremendous development of the methods and diagnostic technologies for the discovery of new biomarkers and the molecular studies on diseases and the mechanisms of drug action has been observed. These innovative technologies and therapies bring hope to reduce the spread of disease and improve the results of treatment of diseases, including those considered as incurable. The development of research on new drugs using computer modeling allows us to transfer the results of these studies directly from bench to bedside within the field of translational medicine. Additionally, everyone can benefit from the new molecularly targeted therapy – tailored to the needs of an individual patient. Personalized medicine aims at providing proper diagnosis and treatment in a timely manner

Systems biology: A tool for charting the antiviral landscape

The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as “the antiviral landscape”. Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral responses. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape

Guidelines for translational research in heart failure

Heart failure (HF) remains a major cause of death and hospitalization worldwide. Despite medical advances, the prognosis of HF remains poor and new therapeutic approaches are urgently needed. The development of new therapies for HF is hindered by inappropriate or incomplete preclinical studies. In these guidelines, we present a number of recommendations to enhance similarity between HF animal models and the human condition in order to reduce the chances of failure in subsequent clinical trials. We propose different approaches to address safety as well as efficacy of new therapeutic products. We also propose that good practice rules are followed from the outset so that the chances of eventual approval by regulatory agencies increase. We hope that these guidelines will help improve the translation of results from animal models to humans and thereby contribute to more successful clinical trials and development of new therapies for HF.European Union [CardioNeT-ITN-289600, CardioNext-ITN-608027, FP7-IMI-JU-SAFET-115003]; Spanish Ministry of Economy [SAF2012-31451]; Regional Government of Madrid [2010-BMD-2321]; Spanish Ministry of Economy; Pro-CNIC Foundation; NIH [HL-120732, HL100401]; AHA [14SFRN20740000]; CPRIT [RP110486P3]; Leducq Foundation [11CVD04]; MINECO-SAF [2013-42962R]; Instituto Carlos III [TERCEL-RD-12/00190026, RIC12/00420024]S

پزشکی آینده پزشکی سیستمی : پزشکی P4

برای درک جهان بیولوژیک، دانشمندان ناچارند که به سوی ناشناخته¬ها، به ویژه به سوی چالش‌های سترگ پیش روند. چالش‌هایی که با پرسش‌هایی بس سترگ‌تر و پیچیده همراه هستند. سیستم‌های بیولوژیک از قوانین حاکم بر سیستم‌های پیچیده پیروی می‌کنند. یک سیستم پیچیده دارای تعداد زیادی اجزای بر هم کنش است که فعالیت انباشتی آنها نمایی غیر خطی داشته و به شکل آشکار تحت فشارهای خاصی نیز رفتار ”خود سازماندهی“ از خود نشان می‌دهند. برای مدل سازی هر رفتار پیچیده، ما می‌بایست از اجزاء تشکیل دهنده‌ی جدا از هم آن (زیرسیستم‌ها) و نیز الگوی پیچیده‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌¬ی ”خود سازماندهی“ که از بر هم کنش این اجزاء خاص می‌آیند، آگاهی داشته باشیم. تاکنون اساس روش شناخت فرایندها بر پایه‌ی روش‌های استقرایی و خرد کردن سیستم به اجزاء تشکیل دهنده‌ی آن و بررسی روابط خطی آنها بوده است. هر چند در پنج سده‌ی گذشته، بشر توانسته است بر این پایه به پیشرفت‌های بسیار بزرگی نایل شود ولی طیّ چند دهه‌ی گذشته‌ پی برده است که این شیوه، پاسخگوی شناخت سیستم‌های پیچیده مانند سیستم‌های بیولوژیک نیست و از این رو کم کم تفکر سیستمی در کاوش‌های علمی، راه خود را باز نموده است. در حقیقت تفکر سیستمی، رهیافتی بسیار فرا دقیق برای دریافت روابط غیر خطی است که روش‌های استقرایی در علم، توان دریافت آنها را ندارند. بنابراین تفکر سیستمی، بینش درک ماهیت کل سیستم را امکان پذیر می‌سازد؛ با درکی که نمی‌توان بر پایه‌ی مطالعه‌ی مجزای اجزای سیستم به دست آورد. بدین سان تفکر سیستمی یک پارادایم است که پیوستگی‌های میان اجزاء گوناگون و بر هم کنش آنها را تحت رصد قرار می‌دهد

Patient preferences of genomic testing in precision cancer medicine

Aims: The aim of this thesis was to identify and rate themed patient preference attributes of genomic testing in precision cancer medicine (PCM). The effect of clinical treatment intent and time since completing treatment was examined as a novel hypothesis that these factors influence identified preference attribute themes and/or ratings. This thesis then benchmarked the identified preference attributes against the ATLANTIS clinical trial design, in order to assess how a current clinical trial incorporates patient preferences. Methods: A narrative review of current cancer treatment paradigms was undertaken alongside systematic review of the literature assessing patient preferences of genomic testing in PCM. In addition, mixed methods research, using Nominal Group Technique (NGT), identified and rated preference attribute themes of genomic testing amongst cancer patients. These preference attributes were then benchmarked against genomic testing undertaken within the ATLANTIS clinical trial, to determine how a novel PCM study design incorporated the attributes. Results: Patient preferences of genomic testing in PCM are influenced by clinical treatment intent and time since completing treatment. Patients undergoing cancer treatment with radical intent demonstrated higher preference ratings for test sensitivity (true positive) and specificity (true negative). Invasiveness of testing and test turnaround time were higher rated preference attributes amongst patients undergoing treatment with palliative intent. Ten preference attribute themes of genomic testing were identified: regulatory/NHS approval, test turnaround time, invasiveness of testing, physician approval, test sensitivity (true positive), test specificity (true negative), prevalence of variant, distance to travel, implications for family and family endorsement for testing. The novel adaptive design of the ATLANTIS trial incorporated many of the preference attribute themes of genomic testing demonstrated in this thesis. Conclusions: Patient preferences of genomic testing in PCM are influenced by clinical treatment intent. This thesis identified and rated preference attribute themes of genomic testing for patients, as well as benchmarking these against a current UK PCM clinical trial. The adaptive design of the ATLANTIS trial incorporated many of the preference attributes, but does not allow for assessment of interaction between multiple inter-related attributes. The results of this thesis augment novel clinical trial design for studies incorporating genomic testing in order they retain patient-centred values at their core

La médecine génomique en santé internationale : le rôle des projets internationaux de science ouverte en génomique

Certaines applications thérapeutiques de la médecine génomique sont susceptibles de mener à une amélioration considérable de la santé des populations des pays en développement dans les années à venir. La mise en place de politiques d’innovation efficaces demeure toutefois cruciale afin d’assurer la réalisation des promesses de la révolution génomique. Dans le domaine biomédical, la commercialisation des fruits de la recherche s’est établie comme le paradigme dominant au sein du système d’innovation. Plusieurs études récentes ont cependant démontré que l’emphase mise sur la commercialisation et la protection de la propriété intellectuelle a donné lieu à des résultats décevants. Certains acteurs du système d’innovation avancent donc désormais qu’il est nécessaire d’aller au-delà de la commercialisation de la recherche et de mettre en place des politiques basées sur le paradigme de la valorisation de la recherche, qui favorise l’atteinte d’objectifs sociaux ainsi qu’économiques. L’objectif de notre mémoire est de documenter l’impact des politiques d’innovation de projets internationaux de science ouverte en génomique médicale sur le développement des capacités en recherche et développement en génomique et l’accès à la médecine génomique dans les pays en développement. Nous avons ainsi réalisé une étude de cas impliquant quatre projets internationaux de science ouverte en génomique médicale. Les résultats de notre étude de cas ont démontré que ces projets jouent un rôle important dans le développement des capacités en recherche et en développement en génomique dans les pays en développement, mais qu’ils y jouent un rôle beaucoup plus limité sur le plan de l’accès aux applications de la médecine génomique.Some therapeutic applications of genomic medicine are likely to lead to considerable improvement in the health care of developing countries in the coming years. However, the establishment of efficient innovation policies remains vital in order to ensure the progress of the genomic revolution. In the biomedical field, the commercialisation of the results of research has established itself as the dominant paradigm in the innovation system. However, many recent studies have demonstrated that this emphasis on commercialisation and the protection of intellectual property has led to deceiving results. Some stakeholders of the innovation system thus argue that it is now necessary to go beyond the commercialisation of research and implement policies based on the research valorisation paradigm, which supports the achievement of social as well as economic objectives. The objective of our thesis is to document the impact of international open science genomic medicine projects’ innovation policies on research and developement in genomics capacity building and access to genomic medicine in developing countries. We have thus developed a case study involving four international open science genomic medicine research projects. The results of our study have demonstrated that these projects play an important role in research and development in genomics capacity building in developing countries, but play a more limited role with regard to access to genomic medicine in these countries