New statistical methods for PhyloG2P

Developing trait-seeded phylogenetic mixture models to associate genotype with phenotype

Degree type

PhD

Closing date

10 October 2022

Campus

Hobart

Citizenship requirement

Domestic/International

About the research project

This project will develop new mathematical tools to better understand the association between species’ genomes (their genotype) and their observable characteristics (their phenotype). Twenty years on from the first genome projects, the problem of mapping from genotype to phenotype is still one of the 21st century’s grand scientific challenges. Better solutions to this fundamental problem would enable improvements across agriculture, medicine, biotechnology and conservation. While techniques such as GWAS (genome-wide association studies) have found many genes associated with traits of interest, for many traits these studies have not revealed as much as was initially hoped.

Novel methods based on evolutionary trees (phylogenies) are needed to understand gene-trait association if we are to ever understand the ~40% of genes that are currently still of unknown function. The key strength of a phylogenetic approach is that, for a trait which has evolved independently multiple times in evolutionary history, we can look for sequence changes that have evolved repeatedly in association with this trait. This idea has been called PhyloG2P, forward genomics or PhyloGWAS. Initial research suggests that the idea has great promise, but it is currently underexplored and new mathematical and computational techniques are required to make progress.

The aim of this project is to develop new “trait-seeded” mixture models. Given a trait that has changed multiple times across a tree we will deliberately seed a mixture model with edge length perturbations that match the ancestral state of the trait. We will determine how best to perform the ancestral state reconstruction; whether to focus on all DNA variation, only non-synonymous variation, or a ratio of the two; how best to parameterize the perturbation of the edge lengths; and how the performance of the model varies with the number of times the trait has evolved on the tree, and strength of association between the genotype and the phenotype.

Primary Supervisor

Meet Prof Barbara Holland

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

  • a living allowance stipend of $28,854 per annum (2022 rate, indexed annually) for 3.5 years
  • a relocation allowance of up to $2,000
  • a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

If successful, international applicants will receive a University of Tasmania Fees Offset for up to four years.

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Additional eligibility criteria specific to this project/scholarship:

  • Applicants must be able to undertake the project on-campus

Selection Criteria

The project is competitively assessed and awarded.  Selection is based on academic merit and suitability to the project as determined by the College.

Additional essential selection criteria specific to this project:

  • Applicants must already have been awarded a first class Honours degree or hold equivalent qualifications or relevant and substantial research experience in an appropriate sector
  • Applicants must be able to demonstrate strong research and analytical skills
  • Knowledge and skills in optimisation, stochastic modelling, statistics or related areas is required
  • Knowledge and skills in simulation and coding or related area is required

Additional desirable selection criteria specific to this project:

  • Degree-level undergraduate education in maths or a related subject
  • Knowledge and skills in biological mathematics, evolutionary genetics or related area will be highly regarded

Application process

There is a three-step application process:

  1. Select your project, and check you meet the eligibility and selection criteria;
  2. Contact the Primary Supervisor, Prof Barbara Holland to discuss your suitability and the project's requirements; and
  3. Submit an application by the closing date listed above.
    • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
    • As part of your application, you will be required to submit a covering letter, a CV including 2 x referees and your project research proposal.

Following the application closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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