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Home , Genomics

BIOL-UA38:

Lectures 75 minutes, twice per week (Mondays and Wednesdays, 9:30-10:45am)

Recitation 75 minutes, once per week (Wednesday 5:00pm-6:15pm)

Text A Primer of Genome Science, 3rd edition Greg Gibson and Spencer V. Muse (2009, Sinauer) Additional readings of journal articles are listed in the weekly schedule below.

Instructors Kristin Gunsalus ([email protected]) Manpreet Katari ([email protected]) Kourosh Salehi-Ashtiani ([email protected])

Course description Modern biological science has entered a new era in the 21st century. Fueled largely by the Project, unprecedented advances in technology have sparked new fields of study that are impacting society on all levels. The ability to collect vast amounts of genome-scale sequence and functional data (genomics) and to analyze them computationally () is allowing scientists to apply new approaches to unanswered questions and to tackle new questions about the biology of that could not be addressed without it. Familiarity with these fields is thus vital for the next generation of scientists and thinkers with an interest in areas such as public policy, , health, and the environment. This course introduces students to fundamental concepts and hot topics in genome science through lectures and critical reading of current research articles.

Course grades Midterm 1: 20% Midterm 2: 20% Final Exam: 25% (cumulative, with emphasis on last third of course) Homework: 10% Participation: 25% (10% on journal club presentations; 10% recitation; 5% class) Class participation includes attendance, preparedness, and interactivity in both Lectures and Recitations. Lectures: The lectures will often cover subject matter that is not introduced in the textbook; therefore material from the text will be supplemented with recent literature reviews. Assigned reading should be completed prior to each lecture in order to maximize the benefit of the lecture. Students will not be responsible for any material from the text that was not part of the assigned reading. Recitation: The recitation will take the form of a journal club, in which the class will read and discuss research articles from primary literature. For each journal club, study questions will be provided one week in advance to help students focus on extracting the main messages of the articles. Twice during the semester, each student will be expected to prepare an overview of one article and lead the class through a critical reading of it. The TA will set the example by presenting the first week and will outline what is expected of students in leading class discussions. Students will meet with the TA at least once prior to their presentation date in order to help them prepare for their presentations. Homework: Weekly homework assignments will be designed to help students digest the information from the lectures and reading assignments. Homework from the prior week will be due one week from the assignment date. The final grade for homework will reflect the best 10 of 12 assignments. Notes: Reading assignments are not intended as a substitute for lecture, which may introduce new core concepts not addressed in any of the assigned reading. Assigned reading may be subject to change during the semester; any changes will be announced at least one week prior to the date for which they are assigned.

BIOL-UA38: Genome Biology

Course Syllabus

Week 1 Lecture 1 Lecture: Overview and introduction to genomics

Reading Genomes 2, Chapter 1.1 (review of DNA structure) [ NCBI Bookshelf ID: NBK21134 ] The ENCODE (ENCyclopedia Of DNA Elements) Project. The ENCODE Project Consortium. Science 306, 636 (2004); DOI: 10.1126/science.1105136

Lecture 2 Lecture: Next-generation technologies

Reading Gibson & Muse, Emerging Sequencing Methods: the Next Generation (pp. 79-83) Genomes for all. Church G, Scientific American 2006

Recitation 1 Journal Club: Next-generation sequencing. Shendure and Li, Nat Biotech 2008. The expanding scope of DNA sequencing. Shendure and Aiden, Nat Biotech 2012.

Week 2 Lecture 3 Lecture: Genome assembly

Reading Gibson & Muse, pp. 83-95 De novo genome assembly: What every should know. Baker M. Nat Meth 2012. Assembly of large genomes using second-generation sequencing. Schatz MC et al. Genome Res. 2010 20: 1165-1173. DOI:10.1101/gr.101360.109.

Lecture 4 Lecture: Genome structure and composition

Reading Genomes 2, Chapter 1.2,1.3 (Human genome ) [ NCBI Bookshelf ID: NBK21134 ] Gibson & Muse, Structural Features of Genome Sequences (pp 107-113)

Recitation 2 Journal Club: Mobile Elements: Drivers of Genome . Kazazian et al. Science 303, 1626 (2004); DOI: 10.1126/science.1089670.

Week 3 Lecture 5 Lecture: Sequence analysis I: pairwise

Reading Gibson & Muse, Box 2.1: Pairwise sequence alignment (pp 74-77), Exercise 2.2 (p. 78)

Lecture 6 Lecture: Genome annotation, prediction, HMMs

Reading Computational prediction of eukaryotic -coding . Zhang M. Nat Rev Genet 2002. Profile Hidden Markov Models. Eddy S. Bioinf 1998.

Recitation 3 Journal Club: Ascaris suum draft genome. Jex et al. 2011, 479:529-33. DOI:10.1038/nature10553. PMID: 22031327

Week 4 No Lecture HOLIDAY – NO CLASS

Lecture 7 Lecture: Sequence analysis II: comparing multiple sequences

Reading Multiple sequence alignment. Edgar & Batzoglou. Curr Opin Struct Biol 2006. BIOL-UA38: Genome Biology

Recent of multiple sequence alignment algorithms. Notredame C. PLoS Comp Biol 2007.

Recitation 4 Review for Midterm 1

Week 5 Midterm Midterm 1

Lecture 8 Lecture: Origins of heritable disease: SNPs, repeats, duplications and rearrangements

Reading Gibson & Muse, pp. 133-138, 177-186

Recitation 5 Journal Club: Recent segmental duplications in the human genome. Bailey et al., Science 2002. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Walsh et al., Science 2008.

Week 6 GuestLecture Lecture: Phyogenetics and

Reading Gibson & Muse, pp. 119-123 Phylogenomics and the reconstruction of the tree of life. Delsuc et al. Nat Rev Genet 2005.

GuestLecture Lecture: Genomics and human origins

Reading Reconstructing human origins in the genomic era. Garrigan & Hammer. Nat Rev Genet 2006. No evidence of a Neanderthal contribution to modern human . Hodgson & Disotell. Genome Biol 2008. NYTimes article: Signs of Neanderthals mating with humans. [http://www.nytimes.com/2010/05/07/science/07neanderthal.html]

Recitation 6 Journal Club: Evolutionary History and from High-Coverage Whole-Genome Sequences of Diverse African Hunter-Gatherers. Lachance et al. 2012. NYTimes commentary on this article [http://www.nytimes.com/2012/07/27/science/cousins-of- neanderthals-left--in-africa-scientists-report.html?pagewanted=1&_r=1]

Week 7 GuestLecture Lecture: Genome variation and

Reading Gibson & Muse, pp. 138-158 Population genomics: patterns of within populations. Gibson G. Wiley online library [onlinelibrary.wiley.com/doi/10.1002/047001153X.g101105/pdf] Combining population genomics and quantitative : finding the genes underlying ecologically important traits. Stinchcombe & Hoekstra, 2008.

GuestLecture Lecture: Population genomics and disease

Reading Gibson & Muse, pp. 158-177 Finding the missing of complex diseases. Manolio et al., Nat Rev 2009. The mystery of missing heritability: Genetic interactions create phantom heritability. Zuk et al., PNAS 2012.

Recitation 7 Journal Club: Genetic mapping in human disease. Altschuler et al., Science 2008.

BIOL-UA38: Genome Biology

SPRING BREAK – March 18-24

Week 8 Lecture 9 Lecture: Transcriptomics: Measurement and analysis of

Reading Gibson & Muse, pp. 190-225, 231-236 From RNA-seq reads to differential expression results. Oshlack et al., Genome Biol 2010.

Lecture 10 Lecture: Expression as a phenotype: eQTLs

Reading Gibson & Muse, pp. 243-251

Recitation 8 Journal Club: Genetics of gene expression and its effect on disease. Emilsson et al. Nature 2008. Multiclass cancer diagnosis using tumor expression signatures. Ramaswamy et al., PNAS 2001.

Week 10 Lecture 11 Lecture: : high-throughput genetics

Reading Gibson & Muse, pp. 294-316 RNAi screening: new approaches, understandings, and organisms. Mohr & Perrimon. Wiley Interdiscip Rev RNA, 2010. DOI: 10.1002/wrna.110

GuestLecture Lecture: : beyond primary sequence

Reading Genomes 2, Section 8.2: Chromatin modifications and gene expression (http://www.ncbi.nlm.nih.gov/books/NBK21137/#A6866). Combinatorial complexity in chromatin structure and : revisiting the histone code. Rando O, Curr Opin Genet Dev 2012.

Recitation 9 Journal Club: Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Carone et al. Cell 2010.

Week 11 GuestLecture Lecture: methods and applications

Reading Gibson & Muse, pp. 267-280 -based proteomics. Aebersold & Mann. Nature 2003. Quantitative mass spectrometry in proteomics: a critical review. Bantscheff et al., Anal Bioanal Chem 2007.

Lecture 12 Lecture: 3D structure and

Reading Gibson & Muse, pp. 286-294 The impact of structural genomics: Expectations and outcomes. Chandonia & Brenner, Science 2006. Lessons from structural genomics. Terwilliger et al., Ann Rev Physiol 2009.

Recitation 10 Review for Midterm 2

BIOL-UA38: Genome Biology

Week 12 Midterm Midterm 2

Lecture 13 Lecture: mapping: large-scale characterization of biological interactions

Reading Gibson & Muse, pp. 280-286 Networks in . Gunsalus & Rhrissorrakrai, Curr Opin Genet Dev 2011. A probabilistic view of gene function. Fraser & Marcotte, Nat Genet 2004.

Recitation 11 Journal Club: Exploring genetic interactions and networks with yeast. Boone C, Nat Rev Genet 2007. The genetic landscape of a cell. Costanzo et al., Science 2010.

Week 13 Lecture 14 Lecture:

Reading Gibson & Muse, pp. 10-12 Comparative genomics and the evolution of prokaryotes. Abby & Daubin. Trends Microbiol 2007.

GuestLecture Lecture: Understanding communities: and

Reading A primer on metagenomics. Wooley et al. PLoS Comp Biol 2010. Human in health and disease. Pflughoeft & Versalovic, Ann Rev Pathol Mech Dis 2012.

Recitation 13 Journal Club: Structure, function, and diversity of the . The Human Microbiome Consortium Project. Nature 2012.

Week 14 Lecture 15 Lecture: 1: Defining the structure of biological networks

Reading Network biology: understanding the cell’s functional organization. Barabasi & Oltvai. Nat Rev Genet 2004. : a network-based approach to human disease. Barabasi et al. Nat Rev Genet 2011.

Lecture 16 Lecture: Systems Biology 2: Modeling systems and dynamics – gene regulatory and metabolomic networks

Reading Gibson & Muse, pp. 333-343 Learning biological networks: from modules to dynamics. Bonneau R. Nat Chem Biol 2008.

Recitation 12 Journal Club: Network inference in Th17 cells. Bonneau et al. 2012 [in press]

Week 14 GuestLecture Lecture: Plant genomics, evolution and systems biology

Reading Genomic clues to the evolutionary success of polyploid plants. Hegarty & Hiscock, Curr Biol 2008. Insights from the comparison of plant genome sequences. Paterson et al., Ann Rev Plant Biol 2010. Evolutionary genetics of plant adaptation. Anderson et al., Trends Genet 2011.

BIOL-UA38: Genome Biology

Lecture 17 Lecture: and

Reading Pharmacogenetics and pharmacogenomics: Origin, status, and hope for personalized medicine. Kalow W. Pharmacogenomics J 2006. Pharmacogenomics and personalized medicine: Lost in ? Hulot J-S. Genome Med 2010.

Recitation 14 Journal club: personalized medicine and biomedical ethics [ A sampling of current NYTimes news articles, e.g. news coverage by Gina Kolata ]

Week 15 Lecture 18 Lecture: Biomedical ethics in the genomic era

Reading Gibson & Muse, pp. 13-21 From genetic privacy to open consent. Lunshof et al., Nat Rev Genet 2008. Research ethics recommendations for whole-: consensus statement. Caulfield et al., PLoS Biol 2008.

FINAL EXAM