ALFRED: Making Very High Throughput Data Accessible

关于人类基因组的新信息正以惊人的速度从科学研究中获得。这项事业的众多方面之一是对人类群体中存在的基因频率变异的表征。世界种群之间的基因频率差异是这些种群历史上所有与遗传相关的机会和系统事件、过去和现在的种群规模、内婚和外婚交配的相对程度及其随时间的变化、随着疾病环境和气候的变化而发生的自然选择动态以及随着人类在世界各地传播时古代种群的无数细分和合并的净作用的结果。科学家正在积累的人类种群间现存的遗传相似性模式的知识，为研究人员正在努力了解这些不同因素在人类进化中所起作用的许多不同领域提供了有用的信息。这包括人类与其他物种的关系，从微生物到其他类人猿，以及书面历史中反映的世界人口之间较新的关系。在NSF的支持下，耶鲁大学于2000年创建了等位基因频率数据库(Alfred)，该数据库为研究和教育提供了广泛的人类基因变异数据。该奖项将支持3个具体目标，支持将刚刚从各个研究团队获得的数据整合到Alfred中的总体目标，这些研究团队研究了来自世界各地的几个到多达几十个种群的大量人类单核苷酸多态(SNPs)。在这些“超高吞吐量”或VHT项目中研究的SNPs的数量从数十万到大约200万个SNPs分布在人类染色体上。第一个具体目标侧重于通过充分自动化管理过程来极大地扩展Alfred的内容，以促进这些非常大的数据集的添加。来自科学文献的其他数据将继续纳入，优先考虑数据库中尚未列出的人口的SNP结果。该项目的第二个目标是通过改进地理信息系统(地理信息系统)界面，特别是通过在数据的图形显示方面提供更大的灵活性，来提高阿尔弗雷德的教育和研究价值。第三个目标是总体上增强用户友好的界面，以帮助用户访问大量扩展的内容。将创建新的和更灵活的方法，以方便组装和下载巨大的多种群和多标记数据集的有用子集。这些改进还将包括扩展说明性文本和静态图表，以教育用户了解数据库的使用情况以及关于数据库所载信息性质的背景资料。目前，Alfred是一个相当大的数据库，拥有近28万个基因频率表，这些表基于650多个人类群体，对14,700多个多态性进行了非常不均匀的研究，并提供了详细的群体和标记描述以及与其他信息数据库的链接。增加VHT项目的数据将大大增加数据库在多态方面的规模，需要如具体目标2和3中概述的那样进行各种调整，以帮助用户利用丰富的新信息。Alfred的这些改进和扩展将放大这一资源的价值，用于人类学遗传学和许多其他已经利用该数据库的跨学科科学(如考古学、人口学、语言学、法医学、人种学和医学研究)的研究和教育。因此，将加强阿尔弗雷德在教育和跨学科研究方面的各种职能。增强的地理信息系统界面将有助于总结各种新兴学科的信息，如地理遗传学和现有学科，如遗传流行病学。阿尔弗雷德将能够提供更多的参考基因频率，以便与研究人员开发的新数据集进行比较。该数据库还可以通过帮助研究人员专注于遗传标记和人口样本的组合来帮助规划未来的研究，这些组合可以测试各种研究问题，或者确定我们知识中需要通过收集新数据集来填补的空白。在最广泛的意义上，阿尔弗雷德的扩展支持了一系列学科和教育努力，旨在更好地了解我们作为一个物种的生物史。此外，打击滥用遗传信息的最有效方法之一是通过像Alfred这样的设施广泛提供关于我们物种遗传变异的数据。

An extraordinary explosion of new information on the human genome is becoming available from scientific research. One of the many facets of this enterprise is the characterization of the variation in gene frequencies that exists among human populations. Gene frequency variation among the world's populations has arisen from the net effect of all the genetically relevant chance and systematic events in the history of those populations past and present population sizes, the relative degree of endogamous and exogamous mating practices and how they varied over time, natural selection dynamics as the disease environment and climate changed, and the numerous subdivisions and mergers of ancient populations as humans spread around the world. The knowledge scientists are accumulating of the extant patterns of genetic similarity among human populations provides useful information to the many different areas where researchers are working to understand the roles those diverse factors have played in human evolution. This includes human relationships with other species from microbes to the other great apes as well as the more recent relationships among the human populations of the world as reflected in written histories. The Allele Frequency Database (ALFRED), created at Yale University in 2000 with support from NSF, makes data on human genetic variation broadly available for research and education. This award will support 3 specific aims supporting the overall goal of integrating into ALFRED the data just now becoming available from various research teams studying enormous numbers of human single nucleotide polymorphisms (SNPs) on a few to as many as several dozen populations from around the world. The number of SNPs studied in these 'very high throughput' or VHT projects ranges from several hundred thousand to about 2 million SNPs distributed across the human chromosomes. The first specific aim focuses on greatly expanding the contents of ALFRED by automating the curation process sufficiently to facilitate the addition of these very large data sets. Other data from the scientific literature will continue to be incorporated with priority given to SNP results from populations not already represented in the database. The second aim of this project enhances the educational and research value of ALFRED by improving the Geographic Information System (GIS) interface, especially by allowing greater flexibility in the graphical display of data. The third aim is to enhance the user-friendly interface generally in order to help users access the vastly expanded contents. New and more flexible methods will be created to facilitate assembling and downloading useful subsets of the huge multi-population and multi-marker datasets. These improvements will also include expanding the explanatory text and static graphics for educating the users about the use of the database as well as background information on the nature of the information contained in the database. Currently, ALFRED is a fairly large database with almost 280,000 gene frequency tables based on more than 650 human populations studied very unevenly on more than 14,700 polymorphisms along with detailed population and marker descriptions and links to other informative databases. The addition of the data from the VHT projects will vastly increase the scale of the database on the polymorphism dimension requiring a variety of adjustments to help users as outlined in specific aims 2 and 3 in order to take advantage of the wealth of new information. These improvements and expansions to ALFRED will magnify the value of this resource for research and education in anthropological genetics and many other interdisciplinary sciences (such as archaeology, demography, linguistics, forensics, ethnography, and medical research) that already make use of the database. ALFRED thus will be strengthened in the service of a variety of functions for education and for interdisciplinary research. The enhanced GIS interface will help summarize information for various emerging new disciplines such as geographical genetics and existing disciplines such as genetic epidemiology. ALFRED will be able to provide even more reference gene frequencies for comparison with new data sets that researchers develop. The database can also assist in the planning of future studies by helping researchers focus on combinations of genetic markers and population samples that can test various research questions or to identify gaps in our knowledge that need to be filled in by collecting new datasets. In the broadest sense, the expansion of ALFRED supports a wide array of disciplines and educational efforts aimed at providing a better understanding of our biological history as a species. Additionally, one of the most effective means to combat the misuse of genetic information is to make data regarding genetic variation in our species widely available through facilities like ALFRED.