Associate Professor Minh Bui.
Computer science can turbocharge research in other fields, from biology and sociology to astronomy and agriculture. For ANU School of Computing Associate Professor Minh Bui, applying statistical and algorithmic models to biology has led to major breakthroughs that put his lab’s computational biology software, IQ-TREE, at the heart of phylogenetics research around the globe, with citations in over forty thousand academic papers.
Phylogenetics explores the history of life through evolutionary genetic trees. Using computational models applied to genomic data, IQ-TREE can reconstruct evolutionary relationships among organisms, from viruses to human beings.
When Bui started work on IQ-TREE in 2013, it was a late addition to the field of phylogenetics. Although other methods existed for constructing phylogenetic trees, Bui saw their limitations and wanted to solve them.
“Science is about diversity,” Bui said. “It is beneficial for the community to have several methods to address the same question.”
Though IQ-TREE uses a classical statistical approach called maximum likelihood estimation that has existed for a long time, Bui and his team of international collaborators made significant leaps in better analysing data and scaling to larger genomic datasets.
Since its initial publication in 2015, IQ-TREE is one of the most used tools in phylogenetics, with hundreds of thousands of users and over one million downloads.
Computing can be used to solve many medical and biological questions. For computing folks, I would say don’t be scared of biology. Once you understand the biological question, you are going to transform it into a computational problem. The main challenge as a researcher is finding the right question to work with.
Informing pandemic-era public health policy
Together with ANU Research School of Biology Professor Robert Lanfear, Bui developed and released IQ-TREE 2 in 2019. The program found use in understanding SARS-CoV-2 virus and its subsequent variants. IQ-TREE 2 informed public health policymaking from the Australian Government to the World Health Organization.
“The media talked about new variants, starting from Alpha to Delta and then Omicron,” Bui explained. “The question is how researchers found these variants. They have to analyse the genomes of virus samples from different patients and then build a phylogenetic tree from the samples. We can see clear groupings of samples with common mutations and isolate the variant. To build this tree, they use IQ-TREE 2.”
In 2023, the Australian Museum awarded Bui and Lanfear with the Australian Research Data Commons Eureka Prize for Excellence in Research Software for their work on IQ-TREE 2.
The latest iteration, IQ-TREE 3, continues a pattern of refinement and improvement of the underlying models and analytic features. Part of its success also stems from its user-centric experience, with extensive manuals and tutorials.
“I remember spending time answering at least 1500 user questions via emails and forums until mid-2024,” Bui said. “We now have a user community on GitHub. The community organises training workshops for IQ-TREE a few times per year.”
Mentorship key to academic success
The Minh Bui and Robert Lanfear labs team photo.
Bui and his post-doctoral researcher Dr. Nhan Ly-Trong were co-authors on a paper, “Assessing phylogenetic confidence at pandemic scales,” published last year in Nature that reconstructed Covid-19’s phylogenetic tree with a method that is scalable to millions of virus genomes, something considered impossible until their research.
Mentorship of young researchers like Ly-Trong plays a key role in Bui’s approach, something he attributes to the mentorship of his PhD advisor, Arndt von Haeseler at the University of Vienna.
“He was my role model,” Bui said. “I got to observe how he supervised and worked with students, postdocs, and colleagues. Fast forward to ANU, I was mentored by Professor Robert Lanfear, now a long-term colleague, while Professor Amanda Barnard gave me a lot of tips on how to be a successful academic. An academic is someone who does everything: not just research, but also supervision, teaching, engagement with colleagues. Last year I supervised an Honours student who was nominated for the university medal.”
Interdisciplinary research at the ANU and beyond
An evolutionary genetic tree showing relationships among various organisms.
A second paper, “A robustly rooted tree of eukaryotes reveals their excavate ancestry,” in collaboration with researchers from Canada, France, the United States, and Norway, set out to decipher the early evolution of organisms known as eukaryotes, characterized by cells with a nucleus, which include plants and animals. Using IQ-TREE, the team shed light on the Last Eukaryotic Common Ancestor, the root organism from which all complex lifeforms are descended.
Bui encourages students to find interdisciplinary applications for computing.
“Computing can be used to solve many medical and biological questions,” Bui added. “For computing folks, I would say don’t be scared of biology. Once you understand the biological question, you are going to transform it into a computational problem. The main challenge as a researcher is finding the right question to work with.”
Bui, who moved from Max Perutz Labs in Austria to join the ANU in 2018, the opportunity to work on exciting questions in a collaborative interdisciplinary environment played a key role in his decision to move across the world.
“I’m working at the intersection of biology and computer science,” Bui said. “I have several collaborators in the School of Biology, the School of Medical Research, and Mathematical Sciences Institute. It’s also very important to collaborate internationally. Each of my PhD students is assigned an international collaborator. It makes Australia not feel isolated. We want to work with everyone as a world-leading group.”