CAREER: Algorithms for Next-Generation Genomics

职业生涯：下一代基因组的算法这个项目的目标是为新的和新兴的高通量DNA测序技术开发算法。这些技术正在将DNA测序的成本降低数量级，从而使各种新的应用成为可能。这些新的应用，再加上这些技术产生的DNA序列的不同特征，增加了对高效算法的需求，以解释由此产生的大量DNA序列数据。PI将开发一种新的稳健算法，用于基因组组装和发现DNA序列变异。其中一些算法将依赖于密切相关的参考基因组序列的可用性，而另一些算法将直接从DNA测序机产生的单个DNA序列(即读取)进行从头开始操作。在后一种情况下，PI将设计算法，利用较新的单分子和纳米孔测序技术中可用的更长范围的DNA序列信息。这些算法将保持高度的敏感性和特异性，同时可扩展到数十亿-万亿个核苷酸和数千个基因组。最后，PI将介绍组合算法，用于研究DNA序列的异质混合中的基因组重排。这种混合出现在元基因组学或癌症基因组学中，在这些基因组学中，被测序的DNA是来自不同物种的基因组的混合物，或者分别来自具有不同突变的细胞。PI与生物学家和技术开发人员密切合作，以确保算法的相关性和适用性。同时，该方案中发展的图论、组合优化和概率论中的一些算法和技术也适用于生物学以外的问题。更广泛的影响拟议的研究将与教育部分相结合，包括开展个人基因组学本科研讨会，为高中生提供计算生物学的暑期研究体验，以及将计算生物学模块纳入九年级女生的计算夏令营。非政府组织将继续积极指导和招募本科生和研究生，包括妇女和代表性不足的少数群体。最后，实现算法的软件将通过公共网络服务器免费分发给科学界。

CAREER: Algorithms for Next-Generation GenomicsThe objective of this project is to develop algorithms for new and emerging high-throughput DNA sequencing technologies. These technologies are lowering the cost of DNA sequencing by orders of magnitude and thereby enabling a variety of new applications. These new applications, combined with the varying characteristics of the DNA sequences produced by these technologies, are increasing demand for efficient algorithms to interpret the resulting large volumes of DNA sequence data. The PI will develop a new class of robust algorithms for genome assembly and discovery of DNA sequence variants. Some of these algorithms will rely on the availability of a closely related reference genome sequence, while others will operate de novo directly from the individual DNA sequences (i.e. reads) produced by a DNA sequencing machine. In the latter case, the PI will design algorithms that exploit longer range DNA sequence information available in newer single-molecule and nanopore sequencing technologies. These algorithms will retain high sensitivity and specificity while scaling to billions-trillions of nucleotides and thousands of genomes. Finally, the PI will introduce combinatorial algorithms for the study of genome rearrangements in heterogeneous mixtures of DNA sequences. Such mixtures arise in metagenomics or cancer genomics, where the DNA that is sequenced is a mixture of genomes from different species, or from cells harboring different mutations, respectively. The PI collaborates closely with biologists and technology developers to ensure relevance and applicability of the algorithms. At the same time, some of algorithms and techniques from graph theory, combinatorial optimization, and probability that are developed in the proposal are applicable to problems outside of biology. Broader ImpactThe proposed research will be integrated with an educational component that includes the development of undergraduate seminar in personal genomics, a summer research experience in computational biology for high-school students, and the incorporation of a computational biology module into a summer computing camp for 9th grade girls. The PI will continue to actively mentor and recruit undergraduate and graduate students, including women and underrepresented minorities. Finally, software implementing the algorithms will be freely distributed to the scientific community through a public webserver.