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Biophysics 205: Computational and Functional Genomics

Spring 2020

NOTE: The syllabus is subject to change. Please check for updates.

Date/Topic Reading Faculty
Monday, January 27

Course Overview and Introduction to Genome Sequencing

Genome Sequencing Lecture

Background: Resources: Next-generation Sequencing Review:
  • Goodwin S.
    Coming of age: ten years of next- generation sequencing technologies.
    Nat Rev Genet 2016.
Wednesday, January 29

Transcriptome I

Transcriptional Profiling and Clustering Lecture

Required: Resources:
  • Jain AK.
    Data Clustering: 50 years beyond K-means.
    Pattern Recognition Letters. 2010; 31(8):651-666.
Monday, February 3

Transcriptome II

Required: Resources:
  • Harrow J et al.
    GENCODE: the reference human genome annotation for The ENCODE Project.
    Genome Research. 2012; 22:1760-74.
Wednesday, February 5

Genome Analysis

Genome Analysis Lecture

Required: Background:
  • Zhang MQ.
    Computational prediction of eukaryotic protein-coding genes.
    Nat Rev Genet. 2002; 3(9):698-709.

  • Durbin R et al.
    Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids. (On reserve at Countway and available in the Biophysics office)
    Chapters 1 and 3.
Monday, February 10

Comparative Genomics and Metagenomics


  • Sackton TB et al.
    Convergent regulatory evolution and loss of flight in paleognathous birds.
    Science. 2019; 364:74-78.
    Supplementary Materials

  • Donia M et al.
    A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics.
    Cell. 2014; 158:1402-1414.

  • Pachiadaki MG et al.
    Charting the Complexity of the Marine Microbiome through Single-Cell Genomics.
    Cell. 2019; 169:1623-1635.



  • Altschul SF, Boguski MS, Gish W, Wootton JC.
    Issues in searching molecular sequence databases.
    Nat Genet. 1994 Feb; 6(2):119-29. Review.

  • Altschul SF and Koonin EV
    Iterated profile searches with PSI-BLAST: a tool for discovery in protein databases.
    Trends Biochem Sci. 1998 Nov;23(11):444-7. Review.

  • Eddy SR.
    Profile hidden Markov models.
    Bioinformatics. 1998; 14(9): 755-83.

  • Durbin et al. Biological Sequence Analysis
    Chapter 5
Wednesday, February 12

Genomics and Protein Structures
Required: Resources:
  • Marks DS et al.
    Protein structure prediction from sequence variation.
    Nat Biotechnol. 2012; 30:1072-80.
Monday, February 17 No class - President's Day
Wednesday, February 19

Noncoding RNAomics
Required: Background:
  • Lindberg J et al.
    The plasticity of the mammalian transcriptome.
    Genomics. 2010; 95:1-6.

  • Ulitsky I and Bartel DP.
    lincRNAs: Genomics, Evolution, and Mechanisms.
    Cell. 2013; 154:26-46.

  • Krol J et al.
    The widespread regulation of microRNA biogenesis, function and decay.
    Nat Rev Gen. 2010; 11:597-610.
Monday, February 24

Genetic Variation I

Genetic Variation Lecture

Required: Resources:
Wednesday, February 26

Required: MV
Monday, March 2

Hi-C, DHS, and Histone Modifications

Histone Modifications Mini-Lecture

Required: Resources:
Wednesday, March 4

Sequence Motifs
Required: MB
Monday, March 9

  • Schmidt D et al.
    Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding.
    Science. 2010; 328(5981):1036-40.

  • Osterwalder M et al.
    Enhancer redundancy provides phenotypic robustness in mammalian development.
    Nature. 2018; 554:239-43.

  • Fulco CP et al.
    Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations.
    Nat Genet. 2019; 51:1664-1669.
    Supplementary Materials
Background: Resources:
Wednesday, March 11

Required: Background: Resources:
  • Bogue MA et al.
    Mouse Phenome Database: an integrative database and analysis suite for curated empirical phenotype data from laboratory mice.
    Nucleic Acids Res. 2018; 46:D843-50.
Monday, March 16 No class - Spring Break
Wednesday, March 18 No class - Spring Break
Monday, March 23

Epigenomes and Epitranscriptomes
Required: Resources:
  • Stricker SH et al.
    From profiles to function in epigenomics.
    Nat Rev Gen. 2017; 18:51-66.

  • Skvortsova K et al.
    Functions and mechanisms of epigenetic inheritance in animals.
    Nat Rev Mol Cell Biol. 2018; 19:774-90.
Wednesday, March 25

Proteomics and Mass Spectrometry

Proteomics Lecture

Required: Resources:
  • Aebersol R and Mann M.
    Mass-spectrometric exploration of proteome structure and function.
    Nature. 2016; 537(7620):347-55.
Monday, March 30

Genetic Variation II
Required: SS
Wednesday, April 1 No class - NHGRI Conference (BIG Trainees)
Monday, April 6

RNA Stability and Translation Regulation
DUE @ 11:59PM: 1-page description of proposal idea

  • Jens M and Rajewsky N.
    Competition between target sites of regulators shapes post-transcriptional gene regulation.
    Nat Rev Genet. 2015; 16(2):113-26.

  • Taggart and Li.
    Production of Protein-Complex Components is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes.
    Cell Systems. 2018; 7(6):580-9.
    Supplementary Materials
Wednesday, April 8

Genetic Variation III
Required: Resources: SS
Monday, April 13

Protein Interactions, Modifications, and Networks
  • Garzón et al.
    A computational interactome and functional annotation for the human proteome.
    eLife 2016; 5.

  • Kastritis PL et al.
    Capturing protein communities by structural proteomics in a thermophilic eukaryote.
    Mol Sys Biol. 2017; 13:936.
Wednesday, April 15

Network Analysis
Required: Background:
  • Cowen L et al.
    Network propagation: a universal amplifier of genetic associations.
    Nat Rev Gen. 2017; 18:551-62.
Monday, April 20

Cell-to-Cell Variability
Required: PK
Wednesday, April 22

Genetic Interactions
Required: SS
Monday, April 27

Signaling Dynamics

Signaling Dynamics Mini-Lecture

  • Li C et al.
    Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation.
    Cell Syst. 2018;6(4):409-423.

  • Christodoulou D et al.
    Reserve Flux Capacity in the Pentose Phosphate Pathway Enables Escherichia coli's Rapid Response to Oxidative Stress.
    Cell Syst. 2018;6(5):569-578.
  • Roussel MR and Zhu R.
    Stochastic kinetics description of a simple transcription model.
    Bull Math Biol. 2006; 68(7):1681-1713.

  • Chen WW et al.
    Classic and contemporary approaches to modeling biochemical reactions.
    Genes Dev. 2010; 24(17):1861-1875.
Wednesday, April 29

Chemical Genomics and Drug Discovery
Required: Resources:
  • Overington JP et al.
    How many drug targets are there?
    Nat Rev Drug Discov. 2006; 5(12):993-996.

  • Lyu J et al.
    Ultra-large library docking for discovering new chemotypes.
    Nature. 2019; 566(7743):224-229
Friday, May 1 DUE @ 11:59PM: written proposal (5 pages, single-spaced, including figures but not references)

Monday, May 4 Proposal Presentations
2:30 - 4:45 PM
Wednesday, May 6 Proposal Presentations
1:00 - 4:30 PM

Web contact: Emma Sydir
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