Annual Review of Biomedical Data Science: Genetic studies through the lens of gene networks

Abstract

Understanding the genetic basis of complex traits is a longstanding challenge in the field of genomics. Genome-wide association studies (GWAS) have identified thousands of variant-trait associations, but most of these variants are located in non-coding regions, making the link to biological function elusive. While traditional approaches, such as transcriptome-wide association studies (TWAS), have advanced our understanding by linking genetic variants to gene expression, they often overlook gene-gene interactions. Here, we review current approaches to integrate different molecular data, leveraging machine learning methods to identify gene modules based on co-expression and functional relationships. These integrative approaches, like PhenoPLIER, combine TWAS and drug-induced transcriptional profiles to effectively capture biologically meaningful gene networks. This integration provides a context-specific understanding of disease processes while highlighting both core and peripheral genes. These insights pave the way for novel therapeutic targets and enhance the interpretability of genetic studies in personalized medicine.

Manubot

Manubot is a system for writing scholarly manuscripts via GitHub. Manubot automates citations and references, versions manuscripts using git, and enables collaborative writing via GitHub. An overview manuscript presents the benefits of collaborative writing with Manubot and its unique features. The rootstock repository is a general purpose template for creating new Manubot instances, as detailed in SETUP.md. See USAGE.md for documentation how to write a manuscript.

Please open an issue for questions related to Manubot usage, bug reports, or general inquiries.

Repository directories & files

The directories are as follows:

• content contains the manuscript source, which includes markdown files as well as inputs for citations and references. See USAGE.md for more information.
• output contains the outputs (generated files) from Manubot including the resulting manuscripts. You should not edit these files manually, because they will get overwritten.
• webpage is a directory meant to be rendered as a static webpage for viewing the HTML manuscript.
• build contains commands and tools for building the manuscript.
• ci contains files necessary for deployment via continuous integration.

Local execution

The easiest way to run Manubot is to use continuous integration to rebuild the manuscript when the content changes. If you want to build a Manubot manuscript locally, install the conda environment as described in build. Then, you can build the manuscript on POSIX systems by running the following commands from this root directory.

# Activate the manubot conda environment (assumes conda version >= 4.4)
conda activate manubot

# Build the manuscript, saving outputs to the output directory
bash build/build.sh

# At this point, the HTML & PDF outputs will have been created. The remaining
# commands are for serving the webpage to view the HTML manuscript locally.
# This is required to view local images in the HTML output.

# Configure the webpage directory
manubot webpage

# You can now open the manuscript webpage/index.html in a web browser.
# Alternatively, open a local webserver at http://localhost:8000/ with the
# following commands.
cd webpage
python -m http.server

Sometimes it's helpful to monitor the content directory and automatically rebuild the manuscript when a change is detected. The following command, while running, will trigger both the build.sh script and manubot webpage command upon content changes:

bash build/autobuild.sh

Continuous Integration

Whenever a pull request is opened, CI (continuous integration) will test whether the changes break the build process to generate a formatted manuscript. The build process aims to detect common errors, such as invalid citations. If your pull request build fails, see the CI logs for the cause of failure and revise your pull request accordingly.

When a commit to the main branch occurs (for example, when a pull request is merged), CI builds the manuscript and writes the results to the gh-pages and output branches. The gh-pages branch uses GitHub Pages to host the following URLs:

• HTML manuscript at https://pivlab.github.io/annual_review_of_biomedical_data_science/
• PDF manuscript at https://pivlab.github.io/annual_review_of_biomedical_data_science/manuscript.pdf

For continuous integration configuration details, see .github/workflows/manubot.yaml.

License

Except when noted otherwise, the entirety of this repository is licensed under a CC BY 4.0 License (LICENSE.md), which allows reuse with attribution. Please attribute by linking to https://github.com/pivlab/annual_review_of_biomedical_data_science.

Since CC BY is not ideal for code and data, certain repository components are also released under the CC0 1.0 public domain dedication (LICENSE-CC0.md). All files matched by the following glob patterns are dual licensed under CC BY 4.0 and CC0 1.0:

• *.sh
• *.py
• *.yml / *.yaml
• *.json
• *.bib
• *.tsv
• .gitignore

All other files are only available under CC BY 4.0, including:

• *.md
• *.html
• *.pdf
• *.docx

Please open an issue for any question related to licensing.