This class is listed as a "HST.S56: Special Graduate Subject: Medical Engineering and Medical Physics" with unspecified units. Please register for 6 units.

Course description: Critical reading of papers that leverage public data related to medical and environmental microbiology. Covers all types of publicly available microbial sequence and phenotypic data, including both metagenomics and traditional isolate-based genomes. Focuses on the key insights that were needed to arrive at a result that anyone with a computer would have had access to and how to frame good questions, in addition to methodological approaches and critiques. Senior undergraduates are welcome.

Format: Weekly discussions of papers, led by students, with occasional introductory lectures by Prof Lieberman. Each class will cover 1-2 published papers. When we discuss preprints, we may use the second half of class collaborating on a comment to be posted on the preprint server. 

Assignments:  For each discussed paper, post 1 or more questions in a google doc by 9p the night before.  Lead discussion of 2-4 papers over the course of the semester (depending on class size) and participate in all class discussions.

Grading: Pass/Fail 

Auditing: Graduate students and undergraduate students must register for the class to participate. Employees (postdocs, research technicians) interested in auditing the class will be expected to participate fully, including presenting papers and posting discussion questions. Please register your interest in auditing the class here.

List of potential papers (syllabus will dynamically evolve based on student interest):

Discovery of an overlooked phage and its ecology:

A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes (2014)

Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages (2020)

Basic understanding of phage and MGE biology from sequence analysis: 

Widespread stop-codon recoding in bacteriophages may regulate translation of lytic genes (2022)

Restriction-modification systems have shaped the evolution and distribution of plasmids across bacteria (2023)

Machine learning (will one of these, or both over two sessions):

Discovery of a structural class of antibiotics with explainable deep learning (2023)

Evolutionary-scale prediction of atomic-level protein structure with a language model (2023)

Determinants of evolutionary rate:

Why highly expressed proteins evolve slowly (2005)

Why Genes Evolve Faster on Secondary Chromosomes in Bacteria (2010)

Detecting associations with metadata (1-2 sessions with some or all these papers):

Meta-analysis of gut microbiome studies identifies disease-specific and shared responses (2017)

Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases (2024)

Environmentally dependent interactions shape patterns in gene content across natural microbiomes (2024)

Role of warfare in ecology of gut microbiome:

The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition (2017)

Human gut bacteria contain acquired interbacterial defence systems (2019)

Gene annotation:

Systematic discovery of antiphage defense systems in the microbial pangenome (2018)

Public good exploitation in natural bacterioplankton communities (2021)

Understanding adaptations associated with environmental change. 

Convergent gain and loss of genomic islands drive lifestyle changes in plant-associated Pseudomonas (2019)

Evolution and host-specific adaptation of Pseudomonas aeruginosa (2024)

Understanding ecology:

Two dynamic regimes in the human gut microbiome (2017)

Metagenomic estimation of dietary intake from human stool (preprint)

Trait evolution (some of these in 1-2 sessions):

Global landscape of phenazine biosynthesis and biodegradation reveals species-specific colonization patterns in agricultural soils and crop microbiomes (2020)

Phylogenetic conservatism of functional traits in microorganisms (2013)

A computational screen for alternative genetic codes in over 250,000 genomes (2021)

Big debates in microbial evolution:

Consistent Metagenome-Derived Metrics Verify and Delineate Bacterial Species Boundaries (2020)

Understanding gene flow and movement of mobile elements (some of these in 1-2 sessions):

Whole genome phylogenies reflect the distributions of recombination rates for many bacterial species (2021)

Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of the nosocomial pathogen Klebsiella pneumoniae (2021)

Genetic exchanges are more frequent in bacteria encoding capsules (2018)

Homologous Recombination Shapes the Architecture and Evolution of Bacterial Genomes (2024)

Problems with a high profile cancer microbiome paper (or: what problems to avoid):

Caution regarding the specificities of pan-cancer microbial structure (2023)

Major data analysis errors invalidate cancer microbiome findings (2023)