Dr. Alan Rubin
[Editor's Note: Dr. Rubin was a presenter at the 2024 Mutational Scanning Symposium, May 22 - 24, hosted by the Broad Institute.]
By Sayeh Gorjifard
Alan Rubin was there from the start.
Rubin, who holds a Ph.D. from the University of Washington, is an expert computational biologist currently affiliated with the Walter Eliza Hall Institute in Melbourne. He started his journey in variant effect computational biology during his doctoral studies at the University of Washington Department of Genome Sciences, under the mentorship of Phil Green. During his graduate studies he witnessed the birth of deep mutational scanning (developed by Doug Fowler and Stan Fields) and wanted to help.
Deep mutational scanning (DMS) draws on high-throughput DNA sequencing to assess the functional capacity of a large number of variants of a protein simultaneously. The development of DMS catalyzed a plethora of wet-lab technology to target every aspect of protein functionality. Yet in the early days, the computational tools to analyze such experiments were not keeping pace with the innovation at the bench.
According to Rubin, “if we can empower the bench scientists, then one of the great things that is going to happen is they are going to be able to make discoveries more quickly and efficiently.”
He saw the potential of DMS and jumped at the chance to make Enrich2, a general software tool for processing, analyzing, and visualizing data from deep mutational scanning experiments. Despite its age, the software is still the leading tool for DMS pipelines.
Following the success of Enrich2, Rubin led the development of MaveDB, an international public repository for datasets from Multiplexed Assays of Variant Effect (MAVEs), such as those generated by deep mutational scanning (DMS) or massively parallel reporter assay (MPRA) experiments.
“We want to make it much easier for clinicians and researchers to get hands-on data without having to dig through literature,” he affirms. “We want to standardize everything for clinicians and patients. If we can get all the data organized in one place, with open licensing and open standards, it will make it easier for people to use.”
By laying down the grammar and infrastructure for DMS data dissemination, the dream of personalized genetic healthcare inches closer to reality.
This early work and contributions helped launch the Atlas of Variant Effects (AVE) Alliance, where he is now a member of the executive committee and co-chair of the AVE Data Coordination and Dissemination workstream. He focuses the workstream on developing and implementing data standards to help people share their research and to formalize how data best to report to researchers or clinicians for maximum impact.
As an Australian scientist, Rubin notes how important it is to keep science as an open and international effort.
“By living in Australia, you are somewhat geographically distanced from epicenters of genomics (like in the US and UK),” so it’s important to keep up to date with the technology and data. “These valuable data and resources should be available to those who have less access to funding/infrastructure too.”
Demonstrating his unwavering dedication to open science and the power of MaveDB, Rubin recently delivered a webinar titled “MaveDB: discovery and interpretation of high throughput functional assay data,” targeted at anyone interested in exploring data from MAVE experiments. He also gave an outreach talk for software engineers at PyCon AU 2023 titled “Building a biological database with Python” that offers a peek behind the curtain and describes what it takes to develop and maintain a project like this.
[Sayeh Gorjifard is a Communications Fellow with the Atlas for Variant Effects Alliance and the Brotman Baty Institute. Contact her at sayeh.gorjifard@gmail.com]
