IIBR:Informatics:Toward an Automated RNA-seq Bioinformatician

基因表达的测量-哪些基因在哪些条件下是活跃的-是理解生物系统不可或缺的工具。 从现代基因组测序技术分析基因表达需要使用复杂的软件，如读取映射器，转录组装器和表达丰度估计器。实现这些步骤之一的软件程序通常具有大量的用户可设置的参数，这些参数影响分析算法如何执行。 科学家、生物学家和临床研究人员必须经常手动或通过其他特殊手段调整这些参数。该项目的目标是通过设计和实现一个自动学习基因表达分析软件的高性能参数的框架来自动化这一过程。该项目还旨在开发算法，软件和方法，使这个框架实用和有用。这将使更多的研究人员能够以更少的努力获得高质量的基因表达分析，并且还将能够改进对大型数据集的分析，其中手动调整每个样本的参数是不切实际的。生物学结果的重现性也将得到增强，因为参数的选择明确地交给了自动化、可重复的过程。这项研究将使涉及基因表达的生物学研究更加准确，成本更低。计划为不同层次的学生（小学到大学）开展一些教育和推广活动，以提高社区对基因表达及其分析的理解。开发的过程将在几个包装工具中实施，用于参数优化，可以放入现有的RNA-seq分析管道，以提高每个步骤的准确性。 设计这些工具的研究将被分解为几个更容易处理的步骤。第一步是通过分析大量现有的RNA-seq样本，为每个工具学习一组代表性的参数向量。在第二步中，基于贝叶斯优化、遗传算法和分类方法等技术组合的机器学习方法将用于设计技术，以从这些被预测为提供高性能的集合中选择参数向量。在第三步中，将设计和实施用于为自动参数选择提供人类可解释的原理的技术。该系统的设计也将提高我们在生物学其他应用领域的参数优化技术的实际知识。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。

Measurement of gene expression --- which genes are active in which conditions --- is an indispensable tool for understanding biological systems. Analysis of gene expression from modern genomic sequencing technologies requires the use of sophisticated software such as read mappers, transcript assemblers, and expression abundance estimators. A software program implementing one of these steps typically has a large number of user-settable parameters that influence how the analysis algorithm performs. Scientists,biologists, and clinical researchers must often tune these parameters by hand or through other ad hoc means. The goal of this project is to automate this process by designing and implementing a framework for automatically learning high-performing parameters for gene expression analysis software. This project also aims to develop algorithms, software, and methodology to make this framework practical and useful. This will allow more researchers to obtain high-quality gene expression analyses with significantly less effort and will also enable improved analysis of large data sets where per-sample parameter tuning by hand is impractical. Reproducibility of biological results will also be enhanced since the choice of parameters is explicitly ceded to an automated, repeatable process. This research will make biological studies involving gene expression more accurate and less costly. A number of educational and outreach activities for various levels of students (elementary through undergraduate) are planned to enhance community understanding of gene expression and its analysis.The developed processes will be implemented in several wrapper tools for parameter optimization that can be dropped into existing RNA-seq analysis pipelines to improve accuracy at each step. The research to design these tools will be broken down into several more tractable steps. The first step will be learning, for each tool, a collection of representative parameter vectors by analyzing large collections of existing RNA-seq samples. In the second step, machine learning methods, based on a combination of techniques such as Bayesian Optimization, genetic algorithms, and classification approaches, will be used to design techniques to select parameter vectors from these sets that are predicted to offer high performance. In the third step, techniques for providing human-interpretable rationales for the automatic parameter choices will be designed and implemented. The design of this system will also enhance our practical knowledge of techniques for such parameter optimization in other application domains within biology. Results from the project can be founThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.