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Department of Biochemistry profile

Dr David Chyou

PositionPostdoctoral Fellow
DepartmentDepartment of Biochemistry
Research summaryBioinformatics of fungal and microbial genomes

Research

I have a PhD degree in mathematics. My research interests include bioinformatics, biostatistics and genomics, particularly on the analyses of microbial and fungal genomes. I develop and use software to answer fundamental questions about the biology of these organisms. I also have an ongoing research interest in analysing medical big-data.

My current research projects are around the following research themes:

The CRISPR Big-data

CRISPR-Cas system in archaea and bacteria acts as a prokaryotic immune system that incorporates sections of foreign nucleic acid sequences, including phage genomes, as spacers into CRISPR arrays in hosts genomes. In an invasion event, the CRISPR-Cas system uses the spacers to target and degrade foreign nucleic acid sequences that were encountered by the host. The biology of the CRISPR-Cas system makes CRISPR arrays a natural database of invaders including viruses of pathogenic bacteria, that provides valuable information to the healthcare sector and primary industries. My recent research in this direction is around the development of an application that predicts hosts of bacteriophages based on CRISPR biology, CRISPRHost. The algorithm of CRISPRHost has contributed to a Nature publication (Rollie et al., 2020) that investigates 'CRISPR-Cas auto-immunity in bacteria'. Currently, CRISPRHost is used in an agricultural research project that aims to mitigate global warming by reducing ruminal methane production in livestock. Putative methanogen phages that invade the methane-producing microbes were identified by CRISPRHost.

I have also been designing an algorithm to predict guide-crRNA genes (i.e. tracrRNAs), which is an important member of the type-II CRISPR-Cas system (Chyou and Brown, 2019), and is also an important reagent in CRISPR-based genome-editing technologies.

diagram showing CRISPR-Cas pathway

New ways of terminating bacterial gene expression

In bacteria, there are two established transcription termination (TT) mechanisms, rho-dependent termination (RDT) and intrinsic termination (IT). However, experimental findings suggest that a significant proportion of transcription events terminate efficiently in vivo, but do not fit the two established TT mechanisms. This project aims to investigate the hypothetical uncharacterized 3rd-class TT mechanism, which we named it C3T. The project started with the development of a machine-learning (ML) based algorithm, to predict RDT and IT in gene-operon termini. Then, gene-operon termini with neither a RDT nor an IT prediction are putative C3T and will be studied experimentally. In late 2019, Assoc. Prof. Chris Brown, Dr Joe Wade (New York) and I secured a Marsden grant to further develop our ML algorithm for TT classification and to discover the unconventional C3T mechanisms in bacteria. The ML algorithm can now scan for RDT and IT terminators in the whole genome.

This study opens a new field of study in microbial gene-expression, and aids to the discovery of novel targets for antibiotics.

Comparative genomics in fungi

Fungi have a variety of morphologies, but roughly in 2 classes: Mushroom-like fungi have a stipe (stalk) and a pilus (cap), whereas ruffle-like fungi have a fruit body without a stalk, or with only a short stalk. Fungal morphology has evolved quite rapidly, so that mushroom-like fungi and truffle-like fungi can be in the same genus. The Cortinarius genus is a very good example. Also in late 2019, Assoc. Prof. David Orlovich (Botany), Assoc. Prof. Chris Brown, Assoc. Prof. Tina Summerfield (Botany), Dr Johnathan Plett (Sydney) and I secured a Marsden grant to compare genomes and transcriptomes of mushroom-like and truffle-like fungi statistically to identify genes that contribute to the morphological differences in these organisms, and then characterize them experimentally. We hypothesized that such morphological switches, as they have occurred with such frequency in this phylum, are governed by alterations to a common set of genetic and cellular mechanisms.

Recently (2021), this project spinned into a side project that is about the development of a computational pipeline to annotate non-coding RNAs (ncRNA) in fungal genomes. Especially in genomes of edible mushrooms, ncRNA annotations are often missing or incomplete in fungal genomes, and this project aims to address this shortcoming. A complete annotation of coding and non-coding genes aids to the development of better crops and benefits the agricultural sector.

mages of different fungi showing differences between mushroom-like and truffle-like specimens

Funding

Our projects are generously funded by NZ Royal Society Marsden Fund, University of Otago Research Grant, and the Otago Biochemistry Department.

Publications

Nishtala, P. S., & Chyou, T.-y. (2022). An updated analysis of psychotropic medicine utilisation in older people in New Zealand from 2005 to 2019. Drugs & Aging. Advance online publication. doi: 10.1007/s40266-022-00965-8

Chinzowu, T., Chyou, T.-y., & Nishtala, P. S. (2022). Antibacterial-associated acute kidney injury among older adults: A post-marketing surveillance study using the FDA Adverse Events Reporting System. Pharmacoepidemiology & Drug Safety. Advance online publication. doi: 10.1002/pds.5486

Nicholls, C., Chyou, T.-y., & Nishtala, P. S. (2022). Analysis of the adverse nervous system and gastrointestinal events associated with solifenacin in older adults using the US FDA adverse event reporting system. International Journal of Risk & Safety in Medicine. Advance online publication. doi: 10.3233/jrs-210054

Chyou, T.-y., & Nishtala, P. S. (2021). Identifying frequent drug combinations associated with delirium in older adults: application of association rules method to a case-time-control design. Pharmacoepidemiology & Drug Safety, 30, 1402-1410. doi: 10.1002/pds.5292

Nishtala, P. S., Gill, S., & Chyou, T.-y. (2020). Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults. Pharmacoepidemiology & Drug Safety, 29, 1689-1695. doi: 10.1002/pds.5155

Chinzowu, T., Chyou, T.-y., & Nishtala, P. S. (2022). Antibacterial-associated acute kidney injury among older adults: A post-marketing surveillance study using the FDA Adverse Events Reporting System. Pharmacoepidemiology & Drug Safety. Advance online publication. doi: 10.1002/pds.5486

Journal - Research Article

Nicholls, C., Chyou, T.-y., & Nishtala, P. S. (2022). Analysis of the adverse nervous system and gastrointestinal events associated with solifenacin in older adults using the US FDA adverse event reporting system. International Journal of Risk & Safety in Medicine. Advance online publication. doi: 10.3233/jrs-210054

Journal - Research Article

Nishtala, P. S., & Chyou, T.-y. (2022). An updated analysis of psychotropic medicine utilisation in older people in New Zealand from 2005 to 2019. Drugs & Aging. Advance online publication. doi: 10.1007/s40266-022-00965-8

Journal - Research Article

Chyou, T.-y., & Nishtala, P. S. (2021). Identifying frequent drug combinations associated with delirium in older adults: application of association rules method to a case-time-control design. Pharmacoepidemiology & Drug Safety, 30, 1402-1410. doi: 10.1002/pds.5292

Journal - Research Article

Chyou, T.-y., Nishtala, R., & Nishtala, P. S. (2020). Comparative risk of Parkinsonism associated with olanzapine, risperidone and quetiapine in older adults: A propensity score matched cohort study. Pharmacoepidemiology & Drug Safety, 29, 692-700. doi: 10.1002/pds.5007

Journal - Research Article

Nishtala, P. S., & Chyou, T.-y. (2020). Identifying drug combinations associated with acute kidney injury using association rules method. Pharmacoepidemiology & Drug Safety, 29, 467-473. doi: 10.1002/pds.4960

Journal - Research Article

Nishtala, P. S., Gill, S., & Chyou, T.-y. (2020). Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults. Pharmacoepidemiology & Drug Safety, 29, 1689-1695. doi: 10.1002/pds.5155

Journal - Research Article

Rollie, C., Chevallereau, A., Watson, B. N. J., Chyou, T.-y., Fradet, O., McLeod, I., Fineran, P. C., Brown, C. M., … Westra, E. R. (2020). Targeting of temperate phages drives loss of type I CRISPR-Cas systems. Nature, 578, 149-153. doi: 10.1038/s41586-020-1936-2

Journal - Research Article

Chyou, T., & Brown, C. M. (2019). Prediction and diversity of tracrRNAs from type II CRISPR-Cas systems. RNA Biology, 16(4), 423-434. doi: 10.1080/15476286.2018.1498281

Journal - Research Article

Nishtala, P. S., Jamieson, H. A., Hanger, H. C., Chyou, T.-y., & Hilmer, S. N. (2019). Examining the risks of major bleeding events in older people using antithrombotics. Cardiovascular Drugs & Therapy, 33, 323-329. doi: 10.1007/s10557-019-06867-z

Journal - Research Article

Shehreen, S., Chyou, T.-y., Fineran, P. C., & Brown, C. M. (2019). Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species. Philosophical Transactions of the Royal Society B, 374(1772), 20180384. doi: 10.1098/rstb.2018.0384

Journal - Research Article

Nishtala, P. S., Chyou, T.-y., Held, F., & Le Couteur, D. G. (2018). Association rules method and big data: Evaluating frequent medication combinations associated with fractures in older adults. Pharmacoepidemiology & Drug Safety, 27(10), 1123-1130. doi: 10.1002/pds.4432

Journal - Research Article

Nishtala, P. S., & Chyou, T.-y. (2017). Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions. Journal of Clinical Pharmacy & Therapeutics, 42(2), 189-194. doi: 10.1111/jcpt.12491

Journal - Research Article

Nishtala, P. S., & Chyou, T.-y. (2017). Real-world risk of diabetes with antipsychotic use in older New Zealanders: A case-crossover study. European Journal of Clinical Pharmacology, 73(2), 233-239. doi: 10.1007/s00228-016-2158-2

Journal - Research Article

Nishtala, P. S., & Chyou, T.-y. (2017). Zopiclone use and risk of fractures in older people: Population-based study. Journal of the American Medical Directors Association, 18(4), 368.e1-368.e8. doi: 10.1016/j.jamda.2016.12.085

Journal - Research Article

Nishtala, P. S., Gnjidic, D., Chyou, T., & Hilmer, S. N. (2016). Discontinuation of statins in a population of older New Zealanders with limited life expectancy. Internal Medicine Journal, 46(4), 493-496. doi: 10.1111/imj.13024

Journal - Research Article

Salahudeen, M. S., Chyou, T.-y., & Nishtala, P. S. (2016). Serum anticholinergic activity and cognitive and functional adverse outcomes in older people: A systematic review and meta-analysis of the literature. PLoS ONE, 11(3), e0151084. doi: 10.1371/journal.pone.0151084

Journal - Research Article

Chyou, T., Liddell, G. F., & Paulin, M. G. (2011). An upper-body can improve the stability and efficiency of passive dynamic walking. Journal of Theoretical Biology, 285(1), 126-135. doi: 10.1016/j.jtbi.2011.06.032

Journal - Research Article

Chyou, D. T., Rawle, V. L., & Trotman, C. N. A. (2007). Quaternary structure of Artemia haemoglobin II: Analysis of T and C polymer alignment and interpolymer interface. BMC Structural Biology, 7, 26. doi: 10.1186/1472-6807-7-26

Journal - Research Article

Christodoulos, I. N., Chyou, T.-y., & Nishtala, P. S. (2020). Safety of fluoxetine use in children and adolescents: A disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database. European Journal of Clinical Pharmacology, 76, 1775-1776. doi: 10.1007/s00228-020-02970-5

Journal - Research Other

Nishtala, P. S., Allore, H., Han, L., Jamieson, H. A., Hilmer, S. N., & Chyou, T.-y. (2020). Impact of anticholinergic burden on cognitive performance: A cohort study of community-dwelling older adults. Journal of the American Medical Directors Association, 21, 1357-1366. doi: 10.1016/j.jamda.2020.03.027

Journal - Research Other

Rees, K. E., Chyou, T.-y., & Nishtala, P. S. (2020). A disproportionality analysis of the adverse drug events associated with lurasidone in paediatric patients using the US FDA Adverse Event Reporting System (FAERS) [Research Letter]. Drug Safety, 43, 607-609. doi: 10.1007/s40264-020-00928-1

Journal - Research Other

Nishtala, P. S., Ndukwe, H. C., Chyou, T.-y., Salahudeen, M. S., & Narayan, S. W. (2017). An overview of pharmacoepidemiology in New Zealand: Medical databases, registries and research achievements. New Zealand Medical Journal, 130(1449), 52-61. Retrieved from https://www.nzma.org.nz/journal

Journal - Research Other

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