清华合成与系统生物学中心
Tsinghua Center for Synthetic and Systems Biology

Detecting and Correcting Spurious Transcriptome Inference due to RNAseq Reads Misalignment

Prof. Wei Wang
Department of Computer Science at University of California at Los Angeles
Host: Xiaowo Wang
Title: Detecting and Correcting Spurious Transcriptome Inference due to RNAseq
Reads Misalignment
Abstract:
RNA-seq techniques provide an unparalleled means for exploring a transcriptome with deep coverage and base pair level resolution. Various analysis tools have been developed to align and assemble RNA-seq data, such as the widely used TopHat/Cufflinks pipeline. A common observation is that a sizable fraction of the fragments/reads align to multiple locations of the genome. These multiple alignments pose substantial challenges to existing RNA-seq analysis tools. Inappropriate treatment may result in reporting spurious expressed genes (false positives), and missing the real expressed genes (false negatives). Such errors impact the subsequent analysis, such as differential expression analysis. In our study, we observed that about 3.5% of transcripts reported by TopHat/Cufflinks pipeline correspond to annotated nonfunctional pseudogenes. Moreover, about 10.0% of reported trascripts are not annotated in the Ensembl database. These genes could be either novel expressed genes or false discoveries. We examined the underlying genomic features that lead to multiple alignments and investigate how they generate systematic errors in RNA-seq analysis. We developed a general tool, GeneScissors, which exploits machine learning techniques guided by biological knowledge to detect and correct spurious transcriptome inference by existing RNA-seq analysis methods. GeneScissors can predict spurious transcriptome calls due to misalignment with an accuracy close to 90%, which represents substantial improvement over the widely used TopHat/Cufflinks or MapSplice/Cufflinks pipelines.
Bio: Dr. Wei Wang is a professor in the Department of Computer Science at University of California at Los Angeles. She received a MS degree from the State University of New York at Binghamton in 1995 and a PhD degree in Computer Science from the University of California at Los Angeles in 1999. She was a professor in Computer Science and a member of the Carolina Center for Genomic Sciences and Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill from 2002 to 2012, and was a research staff member at the IBM T. J. Watson Research Center between 1999 and 2002. Dr. Wang's research interests include data mining, bioinformatics and computational biology, and databases. She has filed seven patents, and has published one monograph and more than one hundred research papers in international journals and major peer-reviewed conference proceedings.
时间: 2013 7 3 日(星期三)上午 10:30 – 12:00 地点: 清华大学FIT大楼 1-312

Two Talks from Prof. Adam Paul Arkin

Prof. Adam Paul Arkin
Director of Physical Biosciences Division at Lawrence Berkeley National Laboratory Dean A. Richard Newton Memorial Professor, Dept of Bioengineering, University of California, Berkeley
Host: Xiaowo Wang Talk One: How will we understand the 10^35 microbes on earth? Towards a Predictive Systems
Biology of Microbes Outside the Laboratory.
The vast acceleration in data gained from genomics and high-throughput genetics is rapidly outstripping our ability to interpret the information and synthesize theories of organismal and community function. We are just now learning experimental designs that best use the big-data capabilities to build predictive models of biological function. Here we will describe progress in these designs and their application to understand diverse environmental microbes and viruses. We will describe new experimental technologies, computational biological tools and new integrative computational infrastructures (notably the systems biology knowledgebase (KBase, http://kbase.us) that we are developing to meet the challenge of understanding the ecological functional and interactions of diverse microbes that perform important environmental, energy and health functions.
Talk Two: Changing Chasses and Inventing Elements: Developing a combined systems biology and engineering approach to designing complex function in cells.
To meet the goal of creating reliable, predictable, efficient, and transparent methods to harness cellular capabilities for human benefit, it is necessary both to have standard libraries of elements from which useful pathways can be constructed and an understanding of the how host physiology and the environment impacts the functioning of these heterologous circuits. We will discuss the challenges in building and characterizing trustworthy synthetic biological applications beyond the bioreactor. We show how variations in cellular and environmental context affect the operation of the basic central dogma functions underlying gene expression. Then we describe progress on creating a complete, scalable, and relatively homogeneous and designable sets of part families that can control central dogma function, signaling, and DNA writing predictably in the face of varying configurations, genetic contexts, and environments.
Bio: Arkin is Division Director of the Physical Biosciences Division at the Lawrence Berkeley National Laboratory and a Full Professor in the Department of Bioengineering, U.C. Berkeley. He is Director of the Synthetic Biology Institute (SBI, http://synbio.berkeley.edu) launched 2010 at Berkeley and Co-Director of the BIOFAB: International Open Facility Advancing Biotechnology (BIOFAB). In addition, he directs the Joint Bioenergy Institute’s Bioinformatics Group and Berkeley Lab’s Virtual Institute of Microbial Stress. He was an investigator with the Howard Hughes Medical Institute (HHMI) until 2007. The thrust of Arkin’s research has focused on developing the physical theory, computational tools and experimental approaches for understanding cellular processes critical to life. The goal is to provide a framework that will facilitate the design and engineering of new functions and behaviors in cells through synthetic and systems biology.
时间: Talk One:2013 7 1 日(星期一)上午 10:00 – 11:30
Talk Two
:2013 7 2 日(星期二)上午 10:00 – 11:30
地点: 清华大学FIT大楼 1-312

Exploration and exploitation of a nisin biosynthesis pathway

Speaker: Prof. Ting Lu, UIUC
Title: Exploration and exploitation of a nisin biosynthesis pathway
Time: 10:00am, Wednesday, June 26
Location: FIT 1-312
Host: Zhen Xie

Biosketch: Dr. Ting Lu is currently an Assistant Professor of Bioengineering and affiliated faculty of the Institute for Genomic Biology at UIUC. His research focuses on the analysis, construction and exploitation of genetic regulatory circuits for bacterial function programming. He received his B.S. in Physics from Zhejiang University, and Ph.D. in Biophysics from UC-San Diego under the supervision of Drs. Peter Wolynes and Jeff Hasty. After that, he pursued a postdoctoral training with Dr. Ron Weiss at Princeton and later MIT. Prior to joining UIUC, he worked with Dr. James Colllins as a postdoctoral fellow at Wyss Institute.

Synthetic Analog and Digital Platforms for Scalable Biological Computation

清华大学合成生物学杰出讲座系列
Tsinghua Distinguished Synbio Seminar Series

Speaker: Timothy K. Lu, MIT
Title: Synthetic Analog and Digital Platforms for Scalable Biological Computation
Location: FIT 1-315
Time: June 21, 10:00 am
Abstract: Scalable platforms for biological computation in living cells would enable new applications in biotechnology and new strategies for studying biological systems. We describe extensible frameworks for implementing digital and analog computation paradigms with synthetic gene circuits. The digital paradigm enables integrated cellular decision-making and logic and can be achieved with libraries of orthogonal recombinases. The analog paradigm enables wide-dynamic-range biosensing and complex mathematical functions with a parsimonious set of devices. We envision that future efforts in synthetic biology will integrate both digital and analog computation to achieve application-specific goals.

合成生物学杰出学者清华会议

合成生物学杰出学者清华会议
Tsinghua Mini-Symposium on Synthetic Biology
2013620日,清华主楼三层接待厅


18届历史悠久的生物化学工程与分子工程国际大会(Biochemical and Molecular Engineering ConferenceBME XVIII)今年在北京举行。BME专注于生物科学与工程交叉领域的前沿研究,是国际生物化学工程和分子工程领域的一个顶级学术会议。今年是该会历史上第二次在美国本土外举行。本次会议的主题之一是合成生物学,有众多的国际著名合成生物学学者包括Jay Keasling参会。

过去十年,国际合成生物学的发展对工业生物技术(含生物化工)、医学生物技术和农业生物技术的影响甚巨,并开始培育了一批以Amyris为代表的Nasdaq上市公司。近年来中国在该领域开始加大基础和应用研究投入,并与美国、英国形成了一个“三国六院(科学院、工程院)会议”的联络机制。


BME XVIII机会,清华大学化工系、生命科学院、信息科学与技术国家实验室、工业生物催化教育部重点实验室联合邀请到了北美、欧洲大陆、英国、韩国等六位有代表性的著名学者,于2013620日,在清华主楼三层接待厅举行合成生物学杰出学者清华会议Jay Keasling教授由于临时需要在BME XVIII会议期间回北美领取重要奖项,无法参加清华会议)。欢迎清华大学和兄弟科研院所的师生参加。

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清华主楼三层接待厅


Tsinghua Mini-Symposium on Synthetic Biology Program

1:45 – 2:00 pm, Welcome remarks
2:00 – 2:35 pm, Ron Weiss, MIT, United States
Synthetic biology: from parts to modules to therapeutic systems
2:35 – 3:10 pm, Jens Nielsen, Chalmers University of Technology, Sweden
Development of platform yeast cell factories through synthetic biology
3:10 – 3:45 pm, Sang Yup Lee, KAIST, Korea
Systems metabolic engineering of microorganisms using synthetic small RNAs
3:45 – 4:00 pm, Tea/coffee break
4:00 – 4:35 pm, Huimin Zhao, UIUC, United States
Synthetic biology: putting synthesis into biology
4:35 – 5:10 pm, Farren Isaacs,Yale, United States
Construction, Characterization & Applications of Genomically Recoded Organisms
5:10 – 5:45 pm, Paul Freemont, Imperial College, United Kingdom
The application of systematic design for the engineering of biological systems - from part characterisation to biosensor design
5:45 – 6:00 pm, Concluding remarks


会议组织者:
林章凛 教授(清华大学化工系、合成生物学973首席科学家、BME分会主席)
谢震 教授(清华大学信息科学与技术国家实验室)
陈国强 教授(清华大学生命学院、合成生物学973首席科学家、BME分会主席)
戴俊彪 教授(清华大学生命学院)
刘铮 教授(清华大学化工系、工业生物催化教育部重点实验室、BME分会主席)
汪小我 教授(清华大学信息科学与技术国家实验室)
于慧敏 教授(清华大学化工系、工业生物催化教育部重点实验室)