Schedule

For the Fall 2023 quarter we will meet twice a week on Tuesday and Thursday at 9:30-12:30 pm in TATA 2501 (Map). Clicking on the topics below will take you to supporting class content including video lectures, hands-on “lab session” sheets, walk-through screencasts, required reading material and homework assignments.


#DateTopics for Fall 2023
0-Getting Oriented
Course introduction, Learning goals & expectations, Meet the instructional team. Setup your computer with required software.
1Tue 10/03/23Welcome to Bioinformatics
Biology is an information science, History of Bioinformatics, Types of data, Application areas and introduction to upcoming course segments, Hands on with major Bioinformatics databases and key online NCBI and EBI resources
2Thu 10/05/23Sequence alignment fundamentals, algorithms and applications
Homology, Sequence similarity, Local and global alignment, classic Needleman-Wunsch, Smith-Waterman and BLAST heuristic approaches, Hands on with dot plots, Needleman-Wunsch and BLAST algorithms highlighting their utility and limitations.
3Tue 10/10/23Project: Find a gene project assignment
(Part 1) Principles of database searching, due in 2 weeks. (Part 2) Sequence analysis, structure analysis and general data analysis with R due at the end of the quarter.
*Tue 10/10/23Optional: Advanced sequence alignment and database searching
Detecting remote sequence similarity, Database searching beyond BLAST, Substitution matrices, Using PSI-BLAST, Profiles and HMMs, Protein structure comparisons as a gold standard.
4Thu 10/12/23Bioinformatics data analysis with R
Why do we use R for bioinformatics? R language basics and the RStudio IDE, Major R data structures and functions, Using R interactively from the RStudio console. Introducing Rmarkdown documents.
5Tue 10/17/23Data exploration and visualization in R
The exploratory data analysis mindset, Data visualization best practices, Simple base graphics (including scatterplots, histograms, bar graphs, dot chats, boxplots and heatmaps), Building more complex charts with ggplot.
6Thu 10/19/23Why, when and how of writing your own R functions
The basics of writing your own functions that promote code robustness, reduce duplication and facilitate code re-use. Extending functionality and utility with R packages from CRAN and BioConductor, Working with Bio3D for molecular data.
7Tue 10/24/23Introduction to machine learning for Bioinformatics 1
Unsupervised learning, K-means clustering, Hierarchical clustering, Heatmap representations. Dimensionality reduction, Principal Component Analysis (PCA)
8Thu 10/26/23Unsupervised learning mini-project
Longer hands-on session with unsupervised learning analysis of cancer cells further highlighting Practical considerations and best practices for the analysis and visualization of high dimensional datasets
9Tue 10/31/23Halloween Candy Mini-Project
A fun and topical mini-project with unsupervised learning analysis of halloween_candy, Practical considerations and best practices for the exploratory analysis and visualization of high dimensional datasets.
10Thu 11/02/23Structural Bioinformatics (pt1)
Comparative structure and sequence analysis. Working with sequence and structure data in R. (If time allows) Protein motion and conformational variants, Molecular simulation and small molecule docking and drug optimization.
11Tue 11/07/23Structural Bioinformatics (pt2 AlphaFold)
The new age of structural biology. Structure prediction with AlphaFold2 and the importance of learning from Multiple Sequence Alignments (MSAs). ESM-Fold and large language models for protein structure.
12Thu 11/09/23Genome informatics and high throughput sequencing
Searching genes and gene functions, Genome databases, Variation in the Genome, High-throughput sequencing technologies, biological applications, bioinformatics analysis methods; The Galaxy platform along with resources from the EBI & UCSC
N.B. This is an online session!
13Tue 11/14/23Transcriptomics, RNA-Seq analysis, and the interpretation of gene lists
RNA-Seq aligners, Differential expression tests, RNA-Seq statistics, Counts and FPKMs and avoiding P-value misuse, Hands-on analysis of RNA-Seq data with R. Gene functional annotation, Functional databases KEGG, InterPro, GO ontologies and functional enrichment.
14Thu 11/16/23RNA-Seq mini project
Differential expression analysis project with DESeq2 followed by gene enrichment and functional annotation with KEGG, InterPro, and GO ontologies.
15Tue 11/21/23Hands-on with Git and GitHub
Why you should use a version control system, How to perform common operations with Git. Creating and working with your own GitHub repos and navagating and using those of others.
16Thu 11/23/23Thanksgiving holiday
No class today. Happy Thanksgiving!
17Tue 11/28/23Essential UNIX for bioinformatics
Bioinformatics on the command line, Understanding processes, File system structure, Connecting to remote servers, Redirection, streams and pipes, Workflows for batch processing, Launching and using AWS EC2 instances (A.K.A. Virtual Machines).
18Thu 11/30/23Analyzing sequencing data in the cloud
A mini-project using AWS EC2 to query, download, decompress and analyze large data sets from the Sequence Read Archive. Practical considerations and best practices for installing bioinformatics software on Linux, transfering large data sets, and performing analysis either locally or on AWS.
19Tue 12/05/23Investigating pertussis resurgence mini project
A topical mini-project using web-scraping,JSON based APIs and advanced dplyr and ggplot to investigate brand new datasets associated with pertussis cases and longitudinal RNA-Seq on the immune response to vaccination.
20Thu 12/07/23Portfolio building and discussion of bioinformatics in industry
Course summary and review, Making a public facing GitHub pages portfolio of your bioinformatics work;
Livestream interview with leading bioinformatics and genomics scientists from industry.
Project: Find a gene assignment due!

Class material

0: Getting oriented

Topics:
Course introduction, Learning goals & expectations, Meet the instructional team. Seting up your computer with required software.

Goals:

  • Understand course scope, expectations, logistics and ethics code.
  • Complete the pre-course questionnaire.
  • Setup your computer for this course.

Videos:

Supporting material:

1: Welcome to Bioinformatics

Topics: Biology is an information science, History of Bioinformatics, Types of data, Application areas and introduction to upcoming course segments, Introduction to NCBI & EBI resources for the molecular domain of bioinformatics, Hands-on session using NCBI-BLAST, Entrez, GENE, UniProt, Muscle and PDB bioinformatics tools and databases.

Goals:

  • Understand the increasing necessity for computation in modern life sciences research.
  • Get introduced to how bioinformatics is practiced.
  • Be able to query, search, compare and contrast the data contained in major bioinformatics databases (GenBank, GENE, UniProt, PFAM, OMIM, PDB) and describe how these databases intersect.
  • The goals of the hands-on session is to introduce a range of core bioinformatics databases and associated online services whilst actively investigating the molecular basis of several common human disease.

Videos:

Supporting Material:

Homework:

2: Sequence alignment fundamentals, algorithms and applications

Topics: Sequence Alignment and Database Searching: Homology, Sequence similarity, Local and global alignment, Heuristic approaches, Database searching with BLAST, E-values and evaluating alignment scores and statistics.

Goals:

  • Be able to describe how dynamic programming works for pairwise sequence alignment.
  • Appreciate the differences between global and local alignment along with their major application areas.
  • Understand how aligning novel sequences with previously characterized genes or proteins provides important insights into their common attributes and evolutionary origins.
  • The goals of the hands-on session are to explore the principles underlying the computational tools that can be used to compute and evaluate sequence alignments.

Videos:

Supporting Material:

Homework:

  • Questions,
  • Submit your completed lab report (i.e. filled in PDF form) to GradeScope,
  • Complete the following Alignment Problem,
  • For next week please install R and RStudio,
  • DataCamp: Sign-up to our F21_Bioinformatics group/organization via the link on Piazza or in your UCSD email. We will use this from next week onward. However, feel free to get started with your first course Introduction to R!.

Readings:


3: (Project) Find a Gene Assignment Part 1

The find-a-gene project is a required assignment for BIMM-143. The objective with this assignment is for you to demonstrate your grasp of database searching, sequence analysis, structure analysis and the R environment that we have covered to date in class.

You may wish to consult the scoring rubric at the end of the above linked project description and the example report for format and content guidance.

  • Your responses to questions Q1-Q4 are due in two weeks time.

  • The complete assignment, including responses to all questions, is due Monday of week 10 at 12pm San Diego time.

  • In both instances your PDF format report should be submitted to GradeScope. Late responses will not be accepted under any circumstances.

Videos:

3: Advanced sequence alignment and database searching

Topics:
Detecting remote sequence similarity, Substitution matrices, Database searching beyond BLAST with PSI-BLAST, Profiles and HMMs, Protein structure comparisons, Beginning with command line based database searches.

Goal:

  • Be able to calculate the alignment score between protein (or nucleotide) sequences using a provided scoring matrix such as BLOSUM62.
  • Understand the limits of homology detection with tools such as BLAST.
  • Know how to derive a PROSITE style regular expression for aligned motifs.
  • Be able to calculate a PSSM profile and for aligned sequences and subsequently score new sequences using a PSSM.
  • Be able to perform PSI-BLAST, HMMER and protein structure based database searches and interpret the results in terms of the biological significance of an e-value.
  • Be familiar with the concepts of True Positives, False Positives, Sensitivity and Specificity.

Material:

Homework:

4: Bioinformatics data analysis with R

Topics: Why do we use R for bioinformatics? R language basics and the RStudio IDE, Major R data structures and functions, Using R interactively from the RStudio console.

Goal:

  • Understand why we use R for bioinformatics
  • Familiarity with R’s basic syntax,
  • Familiarity with major R data structures (vectors, data.frames and lists),
  • Understand the basics of using functions (arguments, vectorizion and re-cycling).

Videos:

Supporting Material:

Homework:

  • Questions,
  • DataCamp: Sign-up to our 24_bioinformatic group/organization via the link in your UCSD email and complete Introduction to R! (4hrs).

5: Data exploration and visualization in R

Topics: The exploratory data analysis mindset, Data visualization best practices, Simple base graphics (including scatterplots, histograms, bar graphs, dot chats, boxplots and heatmaps), Building more complex charts with ggplot.

Goal:

  • Appreciate the major elements of exploratory data analysis and why it is important to visualize data.
  • Be conversant with data visualization best practices and understand how good visualizations optimize for the human visual system.
  • Be able to generate informative graphical displays including scatterplots, histograms, bar graphs, boxplots, dendrograms and heatmaps and thereby gain exposure to the extensive graphical capabilities of R.
  • Appreciate that you can build even more complex charts with ggplot and additional R packages.
  • Be able to write and (re)use basic R scripts to aid with reproducibility.

Videos:

Supporting Material:

Homework:

6: R functions and R packages from CRAN and BioConductor

Topics: The why, when and how of writing your own R functions with worked examples. Further extending functionality and utility with R packages, Obtaining R packages from CRAN and Bioconductor, Working with Bio3D for molecular data, Managing genome-scale data with bioconductor.

Goals:

  • Understand the structure and syntax of R functions and how to view the code of any R function,
  • Be able to follow a step by step process of going from a working code snippet to a more robust function that reduces duplication and facilitate code re-use,
  • Be able to find and install R packages from CRAN and bioconductor,
  • Understand how to find and use package vignettes, demos, documentation, tutorials and source code repository where available.

Videos:

Supporting material:

Homework:

  • Questions,
  • Submit your completed PDF lab report to GradeScope,
  • Write a function: See Q6 of the hands-on lab supplement above. This entails turning a supplied code snippet into a more robust and re-usable function that will take any of the three listed input proteins and plot the effect of drug binding. Note assessment rubric and submission instructions within document.
  • DataCamp: Please work toward completing any outstanding courses including Intro to R, Intro to ggplot2 and Intermediate R.

Other:

7: Introduction to machine learning for Bioinformatics

Topics: Unsupervised learning, supervised learning and reinforcement learning; Focus on unsupervised learning, K-means clustering, Hierarchical clustering, Dimensionality reduction, visualization and analysis, Principal Component Analysis (PCA) Practical considerations and best practices for the analysis of high dimensional datasets.

Goal:

  • Understand the major differences between unsupervised and supervised learning.
  • Be able to create k-means and hierarchical cluster models in R
  • Be able to describe how the k-means and bottom-up hierarchical cluster algorithms work.
  • Know how to visualize and integrate clustering results and select good cluster models.
  • Be able to describe in general terms how PCA works and its major objectives.
  • Be able to apply PCA to high dimensional datasets and visualize and integrate PCA results (e.g identify outliers, find structure in features and aid in complex dataset visualization).

Videos:

Supporting material:

Homework:

Other Material:

8: Unsupervised Learning Mini-Project

Topics: Hands-on project session with unsupervised learning analysis of cancer cells, Practical considerations and best practices for the analysis and visualization of high dimensional datasets.

Goals:

  • Be able to import data and prepare data for unsupervised learning analysis.
  • Be able to apply and test combinations of PCA, k-means and hierarchical clustering to high dimensional datasets and critically review results.

Material:

Homework:

9: Halloween Candy Mini-Project

Topics: A fun and topical mini-project with unsupervised learning analysis of halloween_candy, Practical considerations and best practices for the analysis and visualization of high dimensional datasets.

10: Structural Bioinformatics (pt1)

Topics: Protein structure function relationships, Protein structure and visualization resources, Modeling energy as a function of structure, Homology modeling, AlphaFold, Predicting functional dynamics, Inferring protein function from structure.

Goal:

  • View and interpret the structural models in the PDB,
  • Understand the classic Sequence>Structure>Function via energetics and dynamics paradigm,
  • Be able to use VMD for biomolecular visualization and analysis,
  • Appreciate how AlphaFold has advanced structural bioinformatics,
  • Be able to use the Bio3D package for exploratory analysis of protein sequence-structure-function-dynamics relationships.

Videos:

Material:

Homework:

  • Questions.

11: Structural Bioinformatics (pt2. Focus on new AlphaFold2)

Topics: The new age of structural biology. Structure prediction with AlphaFold2 and the importance of learning from Multiple Sequence Alignments (MSAs). ESM-Fold and large language models for protein structure. Modeling protein energy as a function of structure.

12: Genome informatics

Topics: Genome sequencing technologies past, present and future (Sanger, Shotgun, PacBio, Illumina, toward the $500 human genome), Biological applications of sequencing, Variation in the genome, RNA-Sequencing for gene expression analysis; Major genomic databases, tools and visualization resources from the EBI & UCSC, The Galaxy platform for quality control and analysis; Sample Galaxy RNA-Seq workflow with FastQC and Bowtie2. N.B. This is an online-only class session.

Goals:

  • Appreciate and describe in general terms the rapid advances in sequencing technologies and the new areas of investigation that these advances have made accessible.
  • Understand the process by which genomes are currently sequenced and the bioinformatics processing and analysis required for their interpretation.
  • For a genomic region of interest (e.g. the neighborhood of a particular SNP), use a genome browser to view nearby genes, transcription factor binding regions, epigenetic information, etc.
  • Be able to use the Galaxy platform for basic RNA-Seq analysis from raw reads to expression value determination.
  • Understand the FASTQ file format and the information it holds.
  • Understand the SAM/BAM file format and the information it holds.

Videos:

Supporting material:

Homework:

  • Population analysis: Submit to GradeScope your RMarkdown/Quarto generated PDF with working code, output and narrative text answering Q13 and Q14 in this weeks Hands-on section worksheet.

13: Transcriptomics and the analysis of RNA-Seq data

Topics: Analysis of RNA-Seq data with R, Differential expression tests, RNA-Seq statistics, Counts and FPKMs, Normalizing for sequencing depth, DESeq2 analysis. Gene finding and functional annotation from high throughput sequencing data, Functional databases KEGG, InterPro, GO ontologies and functional enrichment.

Goals:

  • Given an RNA-Seq dataset, find the set of significantly differentially expressed genes and their annotations.
  • Gain competency with data import, processing and analysis with DESeq2 and other bioconductor packages.
  • Understand the structure of count data and metadata required for running analysis.
  • Be able to extract, explore, visualize and export results.
  • Perform a GO analysis to identify the pathways relevant to a set of genes (e.g. identified by transcriptomic study or a proteomic experiment). Use both Bioconductor packages and online tools to interpret gene lists and annotate potential gene functions.

Videos:

Supporting material:

Readings:

Homework:

  • Submit your completed PDF lab report to GradeScope,

14: RNA-Seq analysis mini-project

Topics: Differential expression analysis project with DESeq2 followed by gene enrichment and functional annotation with KEGG, InterPro, and GO ontologies.

15: Hands-on with Git and GitHub

Topics: Today’s lecture and hands-on sessions introduce Git, currently the most popular version control system. We will learn how to perform common operations with Git and RStudio. We will also cover syncing your bioinformatics work to date to GitHub.

Videos:

Supporting material:

Homework:
Submit yoour GitHub class repository URL on GradeScope.

16: Thanksgiving holiday

17: Essential UNIX for bioinformatics

Topics: Bioinformatics on the command line, Why do we use UNIX for bioinformatics? UNIX philosophy, 21 Key commands, Understanding processes, File system structure, Connecting to remote servers, Redirection, streams and pipes, Workflows for batch processing, Organizing computational projects, Going further with your own computer in the cloud, Launching and using AWS EC2 instances (A.K.A. Virtual Machines).

Goals:

  • Understand why we use UNIX for bioinformatics
  • Use UNIX command-line tools for file system navigation and text file manipulation.
  • Have a familiarity with 21 key UNIX commands that we will use ~90% of the time.
  • Be able to connect to remote servers from the command line.
  • Use existing programs at the UNIX command line to analyze bioinformatics data.
  • Understand IO Redirection, Streams and pipes.
  • Understand best practices for organizing computational projects.

Videos:

Supporting material:

Homework:

18: Analyzing sequencing data in the cloud

Topics: A mini-project whre we use bespoke cloud computing resources to query, download, decompress and analyze large data sets from NCBI’s main Sequence Read Archive (SRA). Practical considerations and best practices for installing bioinformatics software on Linux, transfering large data sets, and performing analysis either locally or on AWS.

X: Vaccination rate mini project

Topics: A topical mini-project using ggplot and dplyr on with the latest state wide COVID-19 vaccination data. Practical considerations and best practices for exploratory data analysis.

X: Mutational signatures of cancer mini project.

Topics: A mini-project focussing cancer genomics resources and bioinformatics tools for investigating the molecular basis of cancer and characterization of mutational signatures. Large scale cancer sequencing projects; The Cancer Genome Atlas; the cBioPortal platform; COSMIC; de novo extraction and assignment of mutational signatures.

19: Mini Project: Investigating Pertussis Resurgence

Topics: A topical mini-project using web-scraping, JSON based APIs and advanced dplyr and ggplot to investigate brand new datasets associated with pertussis cases and longitudinal RNA-Seq on the immune response to distinct vaccination strategies.

Homework:

  • Generate a complete lab report with all sections and question responses for submission to gradescope.
  • There are no homework quiz questions this week.

20: GitHub pages, online portfolio completion, GitHub copilot plus bonus Bioinformatics in industry session

Topics: Today’s lecture and hands-on sessions introduce Git, currently the most popular version control system. We will learn how to perform common operations with Git and RStudio. We will also cover making a public facing GitHub pages portfolio of your bioinformatics work. Project assignment troubleshooting. Discussion of Bioinformatics and genomics career opportunities.

Videos:

  • 20.1 - OPTIONAL: Git for humans,
  • 20.2 Introduction to GitHub Pages that we will use for building your portfolio website.
  • 20.3 Live stream interview with leading bioinformatics and genomics scientists from industry including Dr Ali Crawford (Associate Director, Scientific Research, Illumina Inc.), Dr. Bjoern Peters (Full Professor and Principal Investigator, La Jolla Institute) and Dr. Ana Grant (Director of Research Informatics, Synthetic Genomics Inc.).

Supporting material:

Or student topic of choice to be selected from those below:

  • Biological network analysis
  • Cancer genomics
  • Unix tips and tricks for Bioinformatics
  • Structural Bioinformatics and computational drug design
  • Introduction to the tidyverse
  • Writing R packages
  • Advanced RMarkdown
  • Creating online work portfolios with GitHub-pages