Genetic interactions occur when mutations in two or more genes combine to generate an unexpected phenotype. This question is on genetic interaction networks. Read the following papers and their supplementary materials:
- Global mapping of the yeast genetic interaction network, Tong et al., Science 303, 808, 2004
- The genetic landscape of a cell, Costanzo et al., Science, 327, pp. 425-431, 2010
- A global genetic interaction network maps a wiring diagram of cellular function, Costanzo et al., Science, 353, aaf1420, 2016
- Systematic analysis of complex genetic interactions, Kuzmin et al., Science, 360, eaao1729, 2018
The papers report increasingly larger experimental assays of genetic interactions in budding yeast, with the third paper surveying virtually all pairs of genes in this organism and the fourth paper extending the experiments to three-way interactions. Write a critical review and comparison of the four papers focusing on their similarities and differences. You do not need to consider the experimental approaches. Focus on the computational analyses and their results. Points you should consider include:
- How do they define genetic interactions?
- Are any analyses similar in all three papers?
- Are there differences between the papers? There may be two types of differences:
- The papers address the same biological questions but use different computational approaches.
- One paper addresses a biological question that another does not.
- In what way has our knowledge of the cellular machinery in budding yeast improved as we progress from the 2004 paper to the 2010 paper to the 2016 paper to the 2018 paper? Do not discuss specific genes. Focus on higher level trends.
- Let us call the genetic interaction networks in the three papers as \(A\) (2004), \(B\) (2010), \(C\) (2016), and \(D\) (2018), respectively. You should be able to download them from the BioGRID. Run the Spatial Analysis of Functional Enrichment (SAFE) algorithm on these networks. Use this analysis or extend it to discover specific Gene Ontology functions that are enriched only in \(A\), only in \(B\), only in \(C\), or only in \(D\). Describe your approach and summarise your results.
You may consider additional questions that occur to you as you read these papers. You may use images from the papers to make your points. I expect that you will need to read related papers. Be sure to provide appropriate citations and a complete bibliography. Use 11 pt font, single-spaced text, with 1" margins. Your review should be about eight to ten pages long, with at most two pages devoted to the SAFE analysis.