2022 Human Genetic Variation and Disease GRC and GRS

项目摘要 人类变异的广度和复杂性是我们这个时代最大的科学和医学挑战之一。 现代测序技术现在能够详细测量生殖细胞和体细胞的变化，许多 人类疾病的根源变异体可以通过它们在基因组DNA中的位置，进化， 物理化学、结构和功能特性，以及它们对RNA转录物、蛋白质， 分子间相互作用最终，我们必须找到新的方法来量化它们对人类的影响， 细胞组织和生命 为了在2022年解决这一根本挑战，第五届人类遗传变异和疾病戈登 研究会议将汇集来自系统生物学，基因组学， 计算机科学，分子生物学，医学遗传学家，人口遗传学家，数据科学，生物物理学，和 健康信息学专家将在6天内讨论遗传和基因组变异的解释， DNA、RNA和蛋白质水平。然而，这一版本将大大扩大其临床范围，以确保 会议的及时性和重要性。我们现在将把技术重点放在不同的变化上， 他们对免疫系统的明确影响，COVID大流行，与 微生物组、增殖性疾病和早发性疾病，这些病症中的每一种都在 自己的专属会议。每场会议都将在算法进步的前线发表演讲， 分析大数据的人也解释他们在这些特定临床领域的结果。这将反映出越来越多的 翻译相关的基础计算生物学，现在高通量的变异数据正在收集 在庞大的人类群体中（例如，我们所有人，英国生物银行）大规模地进行，并导致一种范式 这些临床主题的变化。这一新设计将系统地实现及时和关键的评估 在每个疾病领域的变异解释的最新技术水平。我们的会议将是独一无二的， 比较和对比在不同患者背景下处理不同变体的各种方法。这将使 与会者在一个特殊的地位，重新评估该领域的现状，并指导未来的这一扩大 该领域基于对证据的仔细阐述和批判性讨论。

Project Summary The breadth and complexity of human variation is one of the great scientific and medical challenges of our time. Modern sequencing technologies now enable detailed measurements of germline and somatic alterations, many of which underlie human disease. Variants can be characterized by their locations in genomic DNA, evolutionary, physicochemical, structural, and functional properties, as well as by their effects on RNA transcripts, proteins, molecular interactions. Ultimately, we must find new methods to measure quantitatively their impacts on human cells, tissues and lives. To address this fundamental challenge in 2022, this fifth Human Genetic Variation and Disease Gordon Research Conference will bring together leading researchers and clinicians from system biology, genomics, computer science, molecular biology, medical geneticist, population geneticist, data science, biophysics, and experts in health informatics who will discuss over 6 days the interpretation of genetic and genomic variants at the DNA, RNA and protein levels. This edition, however, will significantly expand its clinical scope to ensure the timeliness and importance of the meeting. We will now twin the technical focus on diverse variations typical of this meeting to their explicit impact on the immune system, the COVID pandemic, interactions with the microbiome, proliferative disease and early onset diseases, with each of these conditions being addressed in their own dedicated session. Each session will feature speakers at the frontlines of algorithmic advances to analyze big data who also interpret their results in these specific clinical areas. This will reflect the increasing translational relevance of basic computational biology now that high throughput variant data are being gathered on a massive scale across vast human cohorts (All of Us, the UK biobank, for example) and causing a paradigm shift in each of these clinical themes. This new design will systematically enable timely and critical assessment of the state of the art for variant interpretation in each disease area. Our meeting will be unique in the way it will compare and contrast diverse methods that address different variants in different patient contexts. This will put participants in a privileged position to reassess the current state of the field and guide the future of this expanding field based on careful exposition and critical discussion of evidence.