350 Jane Stanford Way A natural experimental design question arises; how should we choose to allocate a fixed sequencing budget across cells, in order to extract the most information out of the experiment? An underlying question for virtually all single-cell RNA sequencing experiments is how to allocate the limited sequencing budget: deep sequencing of a few cells or shallow sequencing of many cells? CS161: Design and Analysis of Algorithms, or equivalent familiarity with algorithmic and data structure concepts. We observe that because clustering forces separation, reusing the same dataset generates artificially low p-values and hence false discoveries, and we introduce a valid post-clustering differential analysis framework which corrects for this problem. out. Interestingly, our results indicate that the corresponding optimal estimator is not the commonly-used plug-in estimator, but the one developed via empirical Bayes (EB). Recognizing that students may face unusual circumstances and require Computational design of three-dimensional RNA structure and function Nat Nanotechnol. Specific problems we will study include genome assembly, haplotype phasing, RNA-Seq quantification, and single-cell RNA-Seq analysis. The best reason to take up Computational Biology at the Stanford Computer Science Department is a passion for computing, and the desire to get the education and recognition that the Stanford Computer Science curriculum provides. David Tse STANFORD UNIVERSITY Introduction Dear Friends, Welcome to the Stanford Artificial Intelligence Lab The Stanford Artificial Intelligence Lab (SAIL) was founded by Prof. John McCarthy, one of the founding fathers of the field of AI. The past ten years there has been an explosion of genomics data -- the entire DNA sequences of several organisms, including human, are now available. Will Computers Crash Genomics? During the first year, the center will present programs on "Genomics and social systems," "Agricultural, ecological and environmental genomics" and "Medical genomics." Single-cell RNA sequencing (scRNA-Seq) technologies have revolutionized biological research over the past few years by providing us with the tools to simultaneously interrogate the transcriptional states of hundreds of thousands of cells in a single experiment. This resulted in a rate-distortion type analysis and culminated in us developing a software called HINGE for bacterial assembly, which is used reasonably widely. Extraordinary advances in sequencing technology in the past decade have revolutionized biology and medicine. When writing up the solutions, students should write the names of people with whom they discussed the assignment. Computational Genomics Extraordinary advances in sequencing technology in the past decade have revolutionized biology and medicine. Let us know if you need some help. total of three free late days (weekends are NOT counted) to use as Use VPN if off campus. This cloud-based platform traverses biological entities seamlessly, accelerating discovery of disease mechanisms to address global public health challenges. Welcome to CS262: Computational Genomics Instructor: Serafim Batzoglou TA: Paul Chen email: cs262-win2015-staff@lists.stanford.edu Tuesdays & Thursdays 12:50-2:05pmGoals of this course • Introduction to Computational ~700 users. Students are expected not to look at the solutions from previous years. Stanford Center for Genomics and Personalized Medicine Large computational cluster. “Valid post-clustering differential analysis for single-cell RNA-Seq”, Jesse M. Zhang, Govinda M. Kamath, David N. Tse, 2019. The area of computational genomics includes both applications of older methods, and development of novel algorithms for the analysis of genomic sequences. some flexibility in the course of the quarter, each student will have a These are long strings of base pairs (A,C,G,T) containing all the information necessary for an organism's development and life. This question has attracted a lot of attention in the literature, but as of now, there has not been a clear answer. Computational genetics and genomics : tools for understanding disease / edited by Gary Peltz. The area of computational genomics includes both applications of older methods, and development of novel algorithms for the analysis of genomic sequences. Room 310, Packard Building “Fast and accurate single-cell RNA-seq analysis by clustering of transcript-compatibility counts”, Vasilis Ntranos, Govinda M. Kamath, Jesse M. Zhang, Lior Pachter, David N. Tse, 2016. Computational genomics analysis service to support member labs and faculty, students and staff. We attempt to close the gap between the blue and green curves in the rightmost plot by introducing the truncated normal (TN) test. We study the fundamental limits of this problem and design scalable algorithms for this. Students may discuss and work on problems in groups of at most three people but must write up their own solutions. Stanford, CA 94305-9515, Helen Niu Hence we studied the complementary question of what was the most unambiguous assembly one could obtain from a set of reads. The problem here is to estimate which of the polymorphisms are on the same copy of a chromosome from noisy observations. African Wild Dog De Novo Genome Assembly We are collaborating with 10X Genomics to adapt their long-range genomic libraries to allow high-quality genome assemblies at low cost. We offer excellent training positions to current Stanford computational and experimental undergraduate, co-term, and masters students. “Optimal Assembly for High Throughput Shotgun Sequencing”, Guy Bresler, Ma’ayan Bresler, David Tse, 2013. These two copies are almost identical with some polymorphic sites and regions (less than 0.3% of the genome). Stanford University School of Medicine: Center for Molecular and Genetic Medicine The CSBF Software Library will be available 24/7. This event provided an opportunity for faculty, students, and SDSI's partners in industry to meet each Program for Conservation Genomics | Stanford Center for Computational, Evolutionary, and Human Genomics Program for Conservation Genomics Enabling the use of genomics in conservation management The remaining major barriers to applying genomic tools in conservation management lie in the complexity of designing and analyzing genomic experiments. You must write the time and date of submission on the assignment. Homework. While several differential expression methods exist, none of these tests correct for the data snooping problem eas they were not designed to account for the clustering process. However, this seemingly unconstrained increase in the number of samples available for scRNA-Seq introduces a practical limitation in the total number of reads that can be sequenced per cell. Stanford Genomics The Stanford Genomics formerly Stanford Functional Genomics Facility (SFGF) provides servcies for high-throughput sequencing, single-cell assays, gene expression and genotyping studies utilizing microarray and real-time PCR, and related services to researchers within the Stanford community and to other institutions. The genome assembly problem is to reconstruct the genome from these reads. The Computational Genomics Summer Institute brings together mathematical and computational scientists, sequencing technology developers in both industry and academia, and biologists who utilize those technologies for research applications. “An Interpretable Framework for Clustering Single-Cell RNA-Seq Datasets”, Jesse M. Zhang, Jue Fan, H. Christina Fan, David Rosenfeld, David N. Tse, 2018. We introduce a method for correcting the selection bias induced by clustering. helen.niu@stanford.edu. It is an honor code violation to write down the wrong time. Stanford, CA 94305-9515, Tel: (650) 723-8121 Electrical Engineering Department Introduction to computational genomics : … thereof). Computational Genomics We develop principled approaches for both the computational and statistical parts of sequencing analysis, motivating better assembly algorithms and single-cell analysis techniques. The TN test is an approximate test based on the truncated normal distribution that corrects for a significant portion of the selection bias. p. ; cm. Applications of these tools to sequence analysis will be presented: comparing genomes of different species, gene finding, gene regulation, whole genome sequencing and assembly. Genomics is a new and very active application area of computer science. In brief, every cell of every organism has a genome, which can be thought as a long string of A, C, G, and T. Assistant Helen Niu Genome Assembly The most important problem in computational genomics is that of genome assembly. These must be handed in at the beginning of class on The IBM Functional Genomics Platform contains over 300 million bacterial and viral sequences, enriched with genes, proteins, domains, and metabolic pathways. We observe that these p-values are often spuriously small. “Partial DNA Assembly: A Rate-Distortion Perspective”, Ilan Shomorony, Govinda M. Kamath, Fei Xia, Thomas A. Courtade, David N. Tse, 2016. To ensure even coverage of the lectures, please sign up to scribe beforehand with one of the course staff. Senior Fellow Stanford Woods Institute for the Environment and Bing Professor in Environmental Science Jonathan’s lab uses statistical and computational methods to study questions in genomics and evolutionary biology. Many high-throughput sequencing based assays have been designed to make various biological measurements of interest. Genomics The Genome Project: What Will It Do as a Teenager? Stanford Data Science Initiative 2015 Retreat October 5-6, 2015 The SDSI Program held its inaugural retreat on October 5-6, 2015. Sequence alignments, hidden Markov models, multiple alignment algorithms and heuristics such as Gibbs sampling, and the probabilistic interpretation of alignments will be covered. In this work, we develop a mathematical framework to study the corresponding trade-off and show that ~1 read per cell per gene is optimal for estimating several important quantities of the underlying distribution. “Community Recovery in Graphs with Locality”, Yuxin Chen, Govinda Kamath, Changho Suh, David Tse, 2016. This … Many high-throughput sequencing based assays have been designed to make various biological measurements of interest. NO FINAL. Cong Lab is developing scalable CRISPR and single-cell genomics technology with computational/data analysis to understand cancer immunology and neuro-immunology. If a student works individually, then the worst problem per problem set will be dropped. This course aims to present some of the most basic and useful algorithms for sequence analysis, together with the minimal biological background necessary for a computer science student to appreciate their application to current genomics research. Electrical Engineering Department Optionally, a student can scribe one lecture. Includes bibliographical references and index. Whenever possible, examples will be drawn from the most current developments in genomics research. We studied the information limits of this problem and came up with various algorithms to solve this problem. Public outreach. Lecture notes will be due one week after the lecture date, and the grade on the lecture notes will substitute the two lowest-scoring problems in the homeworks. Many single-cell RNA-seq discoveries are justified using very small p-values. Tech support will be available during regular business hours via e-mail, chat “HINGE: long-read assembly achieves optimal repeat resolution”, Govinda M. Kamath, Ilan Shomorony, Fei Xia, Thomas A. Courtade, David N. Tse, 2017. The research of our computational genomics group at Stanford Genome Technology Center aims at pushing the boundaries of genomics technology from base pairs to bedside. 2 Computational Biology Group Computational Biology and Bioinformatics are practiced at different levels in many labs across the Stanford Campus. Stanford Libraries' official online search tool for books, media, journals, databases, government documents and more. The most important problem in computational genomics is that of genome assembly. the due date, which will usually be two weeks after they are handed Computer science is playing a central role in genomics: from sequencing and assembling of DNA sequences to analyzing genomes in order to locate genes, repeat families, similarities between sequences of different organisms, and several other applications. GBSC is set up to facilitate massive scale genomics at Stanford and supports omics, microbiome, sensor, and phenotypic data types. Fax: (650) 723-9251 We considered the maximum likelihood decoding for this problem, and characterise the number of samples necessary to be able to recover through a connection to convolutional codes. Founded in 2012, the Center for Computational, Evolutionary and Human Genomics (CEHG) supports and showcases the cutting edge scientific research conducted by faculty and trainees in 40 member labs across the School of Humanities and Sciences and the School of Medicine. and grading weight. three days after its due date. Course will be graded based on the homeworks, We considered this problem and firstly studied fundamental limits for being able to reconstruct the genome perfectly. On the Future of Genomic Data The sequence and de novo assembly … Room 264, Packard Building However, we found that the conditions that were derived here to be able to recover uniquely were not satisfied in most practical datasets. Under no circumstances will a homework be accepted more than Once these late days are exhausted, any homework turned in s/he sees fit. At the center, our group is closely involved in the (NIH Grant GM112625) A student can be part of at most one group. Medical genetics--Mathematical models. Durbin, Eddy, Krogh, Mitchison: Biological Sequence Analysis, Makinen, Belazzougui, Cunial, Tomescu: Genome-Scale Algorithm Design. Want to stay abreast of CEHG news, events, and programs? Students are encouraged to start forming homework groups. More reads can significantly reduce the effect of the technical noise in estimating the true transcriptional state of a given cell, while more cells can provide us with a broader view of the biological variability in the population. State-of-the-art pipelines perform differential analysis after clustering on the same dataset. 350 Jane Stanford Way Copying or intentionally refering to solutions from previous years will be considered an honor code violation. “Optimal Haplotype Assembly from High-Throughput Mate-Pair Reads”, Govinda M. Kamath, Eren Şaşoğlu, David Tse, 2015. Scribing. The course will have four challenging problem sets of equal size Humans and other higher organisms are diploid, that is they have two copies of their genome. ISBN 1-58829-187-1 (alk. Currently 2800+ cores and 7+ Petabytes of high performance storage. A mathematical framework reveals that, for estimating many important gene properties, the optimal allocation is to sequence at the depth of one read per cell per gene. This is an instance of a broader phenomenon, colloquially known as “data snooping”, which causes false discoveries to be made across many scientific domains. Single-cell computational pipelines involve two critical steps: organizing cells (clustering) and identifying the markers driving this organization (differential expression analysis). Students with biological and computational backgrounds are encouraged to work together. He joined Stanford in 2001. Genetics Bioinformatics Service Center (GBSC) is a School of Medicine service center operated by Department of Genetics. “One read per gene per cell is optimal for single-cell RNA-Seq”, M. J. Zhang, V. Ntranos, D. Tse, Nature Communications, 2019. We use Piazza as our main source of Q&A, so please sign up, The lecture notes from a previous edition of this class (Winter 2015) are available, A Zero-Knowledge Based Introduction to Biology, Molecular Evolution and Phylogenetic Tree Reconstruction. First assignment is coming up on January 12th. He received a BS in Computer Science, BS in Mathematics, and MEng in EE&CS from MIT in June 1996, and a PhD in Computer Science from MIT in June 2000. Epub 2019 Aug … In brief, every cell of every organism has a genome, which can be thought as a long string of A, C, G, and T. With current technology we do not have the ability to read the entire genomes, but get random noisy sub-sequences of the genome called reads. paper) 1. If you have worked in an academic setting before, please add If you have worked in an academic setting before, please add … More about Cong Lab 2019 Sep;14(9):866-873. doi: 10.1038/s41565-019-0517-8. We also drew connections between this problem and community detection problems and used that to derive a spectral algorithm for this. Also, when writing up the solutions students should not use written notes from group work. late will be penalized at the rate of 20% per late day (or fraction Interestingly, the corresponding optimal estimator is not the widely-used plugin estimator but one developed via empirical Bayes. Stanford Libraries' official online search tool for books, media, journals, databases, government documents and more. Summary In this thesis we discuss designing fast algorithms for three problems in computational genomics. Existing workflows perform clustering and differential expression on the same dataset, and clustering forces separation regardless of the underlying truth, rendering the p-values invalid. The Stanford Genetics and Genomics Certificate Program utilizes the expertise of the Stanford faculty along with top industry leaders to teach cutting-edge topics in the field of genetics and genomics. Serafim's research focuses on computational genomics: developing algorithms, machine learning methods, and systems for the analysis of large scale genomic data. Cancer Computational Genomics/Bioinformaticist Position - Stanford Situated in a highly dynamic research environment at Stanford University in the Departments of Me... 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