EN.601.452 / AS.020.415 Computational Biomedical Research & Advanced Biomedical Research

Class Hours: Monday + Wednesday @ 3p - 3:50p in Hodson 311
Schatz Office Hours: Monday @ 4-5p in Malone 323 and by appointment
CA: Melanie Kirsche - Office Hours Wednesday @ 9-10 AM in Malone 216 and by appointment

The goal of this course is to prepare undergraduates to understand and perform state-of-the-art biomedical research. This will be accomplished through three main components: (1) classroom-style lectures on cross cutting techniques for biomedical research focusing on data visualization, statistical inference, and scientific computing; (2) research presentations from distinguished faculty on their active research projects; and (3) a major research project to be performed under the mentorship of a JHU professor. Students will present their research during an in-class symposium at the end of the semester. Grading will be based on homework exercises, a written research proposal, an interim research report, an oral research presentation, and a final research report.

Course Resources:

• Syllabus and Policies
• Piazza Discussion Board
• GradeScope Entry Code: MPK8BX

Recommended Prerequisites

• Online introduction to Unix/Linux. Students are strongly recommended to complete one of the following online tutorials before class begins.
  • Code academy's Intro to Unix
  • Command line bootcamp
• Access to a Linux Machine, or Install VirtualBox (Unfortuantely, even Mac will not work correctly for some programs)

Related Courses & Readings

• Applied Comparative Genomics
• Bioinformatics Algorithms: An Active Learning Approach (Compeau and Pevzner)
• Unix and Perl for Biologists (Bradnam et al)
• Molecular Biology of the Gene (Watson et al)
• Molecular Biology of the Cell (Alberts)
• Biological Sequence Analysis (Durbin et al)
• Modern Statistics for Modern Biology (Holmes & Huber)

Schedule

#	Date	Lecture	Readings & Resources	Assignment
1.	Th 8/29	Lecture 1. Introduction	* Biological data sciences in genome research (Schatz, 2015, Genome Research) * Big Data: Astronomical or Genomical? (Stephens et al, 2015, PLOS Biology)	Sign Up for Piazza
	Mon 9/2	🔸 Labor Day Break!
2.	Wed 9/4	Lecture 2. Genome Sequencing	* Coming of age: ten years of next-generation sequencing technologies (Goodwin et al, 2016, Nature Reviews Genetics) * High‐throughput sequencing for biology and medicine (Soon et al, 2013, Molecular Systems Biology)	Assignment 1
3.	Mon 9/9	Lecture 3. Genome Assembly	* De novo genome assembly: what every biologist should know (Baker, 2012, Nature Methods)
4.	Wed 9/11	Lecture 4. The Human Genome	* The Sequence of the Human Genome (Venter et al, 2001, Science) * Initial sequencing and analysis of the human genome (IHGSP, 2001, Nature)	Assignment 2
5.	Mon 9/16	Lecture 5. Whole Genome Alignment	* Versatile and open software for comparing large genomes (Kurtz et al, 2004) Genome Biology
6.	Wed 9/18	Lecture 6. Read Mapping	* How to map billions of short reads onto genomes (Trapnell and Salzberg, 2009, Nature Biotech) * Bowtie: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome (Langmead et al, 2009, Genome Biology) * BWA-MEM: Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM (Li, 2013, arXiv)
7.	Mon 9/23	Lecture 7. Variant Identification	* SAM/BAM/Samtools: The Sequence Alignment/Map format and SAMtools (Li et al, 2009, Bioinformatics) * IGV: Integrative genomics viewer (Robinson et al, 2011, Nature Biotech) * PolyBayes: A general approach to single-nucleotide polymorphism discovery (Marth et al, 1999, Nature Genetics) * GATK: A framework for variation discovery and genotyping using next-generation DNA sequencing data (Depristo et al, 2011, Nature Genetics) * Scalpel: Accurate de novo and transmitted indel detection in exome-capture data using microassembly (Narzisi et al, 2014, Nature Methods)	Assignment 3
8.	Wed 9/25	Lecture 8. Human Evolution	* An integrated map of genetic variation from 1,092 human genomes (1000 Genomes Consortium, 2012, Nature) * Analysis of protein-coding genetic variation in 60,706 humans (Let et al, 2016, Nature) * A Draft Sequence of the Neandertal Genome (Green et al. 2010, Science) * Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals (Vernot et al. 2016. Science)
9.	Mon 9/30	Lecture 9. Human Genetic Diseases	* Genome-Wide Association Studies (Bush & Moore, 2012, PLOS Comp Bio) * The contribution of de novo coding mutations to autism spectrum disorder (Iossifov et al, 2014, Nature)
10.	Wed 10/2	Research Lab 1: How to Give a Talk	Meet in Maryland 217!!!	Project Pitch
11.	Mon 10/7	Faculty Presentation 1	Alexis Battle
12.	Wed 10/9	Faculty Presentation 2	Steven Salzberg
13.	Mon 10/14	Lecture 10. RNA-seq	* RNA-Seq: a revolutionary tool for transcriptomics (Wang et al, 2009. Nature Reviews Genetics) * Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks (Trapnell et al, 2012, Nature Protocols) * Salmon provides fast and bias-aware quantification of transcript expression (Patro et al, 2017, Nature Methods) * Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications (Krueger and Andrews, 2011, Bioinformatics)
14.	Wed 10/16	Lecture 11. Gene Finding & HMMs	* Glimmer: Microbial gene identification using interpolated Markov models * MAKER2: an annotation pipeline and genome-database management tool for second-generation genome projects * What is a hidden Markov model?	Written abstract
15.	Mon 10/21	Lecture 12. Gene Regulation	* ChIP–seq and beyond: new and improved methodologies to detect and characterize protein–DNA interactions (Furey, 2012, Nature Reviews Genetics) * PeakSeq enables systematic scoring of ChIP-seq experiments relative to controls (Rozowsky et al. 2009. Nature Biotech) * Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome (Lieberman-Aiden et al, 2009, Science)
16.	Wed 10/23	Research Lab 2: Proposal Presentations		Project details
17.	Mon 10/28	Regulatory States, ENCODE, GTEx, RoadMap	* An integrated encyclopedia of DNA elements in the human genome (The ENCODE Project Consortium, Nature, 2012) * Genetic effects on gene expression across human tissues (GTEx Consortium, Nature, 2017) * Integrative analysis of 111 reference human epigenomes (Roadmap Epigenome Consortium, Nature, 2015) * ChromHMM: automating chromatin-state discovery and characterization (Ernst & Kellis, 2012, Nature Methods) * Segway: Unsupervised pattern discovery in human chromatin structure through genomic segmentation (Hoffman et al, 2012, Nature Methods)
18.	Wed 10/30	Research Lab 3: Data Requirements
19.	Mon 11/4	Lecture 13. Cancer Genomics	* The Hallmarks of Cancer (Hanahan & Weinberg, 2000, Cell) * Evolution of Cancer Genomes (Yates & Campbell, 2012, Nature Reviews Genetics) * Comprehensive molecular portraits of human breast tumours (TCGA, 2012, Nature)
20.	Wed 11/6	Machine Learning Primer	Preliminary Report
21.	Mon 11/11	Lecture 14. Metagenomics	* Kraken: ultrafast metagenomic sequence classification using exact alignments (Wood and Salzberg, 2014, Genome Biology) * Chapter 12: Human Microbiome Analysis (Morgan and Huttenhower)
22.	Wed 11/13	Lecture 15. Plant Genomics	* Duplication of a domestication locus neutralized a cryptic variant that caused a breeding barrier in tomato (Soyk et al. 2019 Nature Plants * RaGOO: Fast and accurate reference-guided scaffolding of draft genomes (Alonge et al. 2019. Genome Biology)
23.	Mon 11/18	Grad Student Forum
24.	Wed 11/20	Research Lab 4: Presentation Preparation
	Mon 11/25	🔸 Thanksgiving Break!
	Wed 11/27	🔸 Thanksgiving Break!
25.	Mon 11/18	Lecture 16. Genomic Futures	* "Snyderome" Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes (Chen et al, 2012, Cell) * Identifying Personal Genomes by Surname Inference (Gymrek et al, 2013, Science)
26.	Wed 12/4	Research Presentations		Research Presentation
	Wed 12/18	Research Report Due		Research Report Due