Deep Learning in Genomics and Biomedicine

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Course Overview

Recent breakthroughs in high-throughput genomic and biomedical data are transforming biological sciences into "big data" disciplines. In parallel, progress in deep neural networks are revolutionizing fields such as image recognition, natural language processing and, more broadly, AI. This course explores the exciting intersection between these two advances. The course will start with introduction to deep learning and overview the relevant background in genomics and high-throughput biotechnology, focusing on the available data and their relevance. It will then cover the ongoing developments in deep learning (supervised, unsupervised and generative models) with the focus on the applications of these methods to biomedical data, which are beginning to produced dramatic results.  In addition to predictive modeling, the course emphasizes how to visualize and extract interpretable, biological insights from such models. Recent papers from the literature will be presented and discussed. Students will work in groups on a final class project using real world datasets.

Prerequisites

College calculus, linear algebra, basic probability and statistics such as CS109, and basic machine learning such as CS229. No prior knowledge of genomics is necessary.

Lecture Venue and Times

09/25/2017 - 12/09/2017 Mon, Wed 3:00 PM - 4:20 PM at Hewlett Teaching Center 201

Recitation. Fridays 10:30am - 11:20am at 380-380D

Instructors

Anshul Kundaje (Links to an external site.)Links to an external site., Assistant Professor (akundaje@stanford.edu)

James Zou (Links to an external site.)Links to an external site., Assistant Professor ()

 

Office hours

James Zou (Links to an external site.)Links to an external site.: Mondays 4:30-6pm (Packard 253).

Anshul Kundaje: Mondays 4.30-5.30 pm (Lane Med School Building L301)

 

Assignments

Course project (60%): the students will form teams of 3-5 and choose from one of the suggested projects or select their own project. Teams will be given Microsoft Azure credits to implement algorithms and perform analysis. Teams are expected to work on the research project throughout the second half of the quarter and produce conference-style papers. Each team will present the paper to the entire class at the end of the semester. The course project will consists of the following milestones:

  1. Project proposal in class (3 minute talk).
  2. First draft of the paper for peer review. 
  3. Poster presentation (12/11 3:30-6:30pm).
  4. Final paper (due at noon on Friday 12/15). 

A significant portion of the class will be based on reading and discussing the latest literature. Every student should read the assigned papers before class and participate in discussions.

Paper presentation (20%): each team selects one of the suggested papers to present in detail to the class. The presentation should be 20 mins + 5 mins for Q&A. Each team will also write a concise review of the paper. The review will be published on bioRxiv and the Zou group blog. 

Peer project review (10%): each team will be assigned two other groups' paper drafts to review. The review should concisely summarize the key findings of the paper, highlight interesting ideas, weaknesses and give suggestions.

Class participation (10%): every student should actively engage in paper discussions in class. 

Schedule

The first few lectures will cover the basics of deep learning---convolutional and recurrent architectures, generative models, and optimization/regularization. We will also study the applications of deep learning in several biomedical domains---genomics, protein structure, imaging and medical records. 

Date Topic Papers Recitation topic Assignment
9/25 Overview. Intro to machine learning

1. Deep Learning 
http://www.nature.com/nature/journal/v521/n7553/full/nature14539.html
2. Neural Nets and Deep learning primer 
http://neuralnetworksanddeeplearning.com/

(See other readings in Files Section)
9/27 Genomics

1. Neural Nets and Deep learning primer 
http://neuralnetworksanddeeplearning.com/
2. Deep learning for computational biology
http://msb.embopress.org/content/12/7/878

(See other readings in Files Section)

 Deep learning primer
10/2 DenseNets + Convolutional Nets for Genomics

1. Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks http://genome.cshlp.org/content/26/7/990.full

2. Denoising genome-wide histone ChIP-seq with convolutional neural networks
https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btx243

(See other readings in Files Section)
10/4 Recurrent NN 1. DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences
https://www.ncbi.nlm.nih.gov/pubmed/27084946 		Genomics primer Projects released on 10/6.
10/9 Autoencoders + representation learning
10/11 Optimization + regularization
+ Azure Demo		 TensorFlow primer Select projects and papers. 
10/16 Generative models GANs for Biological Image Synthesis
https://arxiv.org/abs/1708.04692
10/18 Instructor led paper presentations

1. Basenji: Sequential regulatory activity prediction across chromosomes with convolutional neural networks
https://www.biorxiv.org/content/early/2017/07/10/161851
2. FIDDLE: An integrative deep learning framework for functional genomic data inference
https://www.biorxiv.org/content/early/2016/10/17/081380
3. DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1189-z

 TensorFlow tutorial 2
10/23 Interpretation of black-box models

1. The Mythos of Model Interpretability
https://arxiv.org/abs/1606.03490
2. DeepLIFT: Learning Important Features Through Propagating Activation Differences
https://arxiv.org/abs/1704.02685v1
3. Deep Motif Dashboard: Visualizing and Understanding Genomic Sequences Using Deep Neural Networks
https://arxiv.org/abs/1608.03644 
10/25 Paper presentations

1. Attend and Predict: Understanding Gene Regulation by Selective Attention on Chromatin
https://arxiv.org/abs/1708.00339
2. Deep learning for population genetics
http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004845
3. Integrative deep models for alternative splicing
https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btx268

 Deep learning review
10/30 Proposal presentations

 

 3 minute proposal presentations
11/1 Guest lecture: Google Brain team

1. DeepVariant: Creating a universal SNP and small indel variant caller with deep neural networks
https://www.biorxiv.org/content/early/2016/12/21/092890
2. Chiron: Translating nanopore raw signal directly into nucleotide sequence using deep learning
https://www.biorxiv.org/content/early/2017/09/12/179531
3. Adaptive Somatic Mutations Calls with Deep Learning and Semi-Simulated Data
https://www.biorxiv.org/content/early/2016/10/04/079087
11/6 Drug discovery + protein structure

1. Deep learning for computational chemistry http://onlinelibrary.wiley.com/doi/10.1002/jcc.24764/abstract
2. MoleculeNet
3. One shot learning drug discovery  
11/8 Paper presentations

1. Accurate De Novo Prediction of Protein Contact Map by Ultra-Deep Learning Model
http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005324
2. De novo peptide sequencing by deep learning
http://www.pnas.org/content/114/31/8247
3. Molecular De Novo Design through Deep Reinforcement Learning
https://arxiv.org/abs/1704.07555
11/13 Paper presentations

1. druGAN: An Advanced Generative Adversarial Autoencoder Model for de Novo Generation of New Molecules with Desired Molecular Properties in Silico http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00346
2. Molecular Graph Convolutions: Moving Beyond Fingerprints https://arxiv.org/abs/1603.00856 ,  

3. Convolutional Networks on Graphs for Learning Molecular Fingerprints
http://papers.nips.cc/paper/5954-convolutional-networks-on-graphs-for-learning-molecular-fingerprints
11/15 Imaging + Electronic Medical Records

1. Deep learning for healthcare: review, opportunities and challenges https://academic.oup.com/bib/article-abstract/doi/10.1093/bib/bbx044/3800524/Deep-learning-for-healthcare-review-opportunities
2. Deep EHR: A Survey of Recent Advances on Deep Learning Techniques for Electronic Health Record (EHR) Analysis https://arxiv.org/abs/1706.03446
3. Predicting Cardiovascular Risk Factors from Retinal Fundus Photographs using Deep Learning
https://arxiv.org/abs/1708.09843v2
11/27 Paper presentations

1. Privacy-preserving generative deep neural networks support clinical data sharing
https://www.biorxiv.org/content/early/2017/07/05/159756.1
2. Dermatologist-level classification of skin cancer with deep neural networks http://www.nature.com/nature/journal/v542/n7639/abs/nature21056.html
3. Medical Concept Representation Learning from Electronic Health Records and its Application on Heart Failure Prediction https://arxiv.org/ftp/arxiv/papers/1602/1602.03686.pdf

 Initial paper submitted for peer review
11/29 Paper presentations

1. Learning to Detect Sepsis with a Multitask Gaussian Process RNN Classifier
http://proceedings.mlr.press/v70/futoma17a/futoma17a.pdf
2. RETAIN: An Interpretable Predictive Model for Healthcare using Reverse Time Attention Mechanism
https://arxiv.org/abs/1608.05745
3. Leveraging uncertainty information from deep neural networks for disease detection
https://www.biorxiv.org/content/early/2017/08/02/084210

 Peer review out
12/4 Paper presentations

1. Learning Sleep Stages from Radio Signals:A Conditional Adversarial Architecture
http://sleep.csail.mit.edu/files/rfsleep-paper.pdf
2. Interpretable Deep Models for ICU Outcome Prediction
http://www-scf.usc.edu/~zche/papers/amia2016.pdf
3. Reconstructing cell cycle and disease progression using deep learning
https://www.nature.com/articles/s41467-017-00623-3 
12/6 Wrap up Opportunities/Obstacles Deep Learning Biomedicine
https://www.biorxiv.org/content/early/2017/05/28/142760
12/11 Finals week: poster presentation Final paper due 12/15. 

Course Summary:

Date Details Due