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28 December 2020 | Story André Damons | Photo Supplied
Dr Michael Pienaar is a lecturer in the University of the Free State’s (UFS) department of Paediatrics and Child Health.

A lecturer from the University of the Free State’s (UFS) department of Paediatrics and Child Health is investigating the use of artificial neural networks to develop models for the prediction of patient outcomes in children with severe illness.

Dr Michael Pienaar, senior lecturer and specialist, is conducting this research as part of his doctoral research and the study deals primarily with the development of models that are designed and calibrated for use in South Africa. These artificial neural networks are computer programs designed to mimic some of the learning characteristics of biological neurons.

The potential applications of models

According to Dr Pienaar these models have traditionally been developed in high-income nations using conventional statistical methods.

“The potential applications of such models in the clinical setting include triage, medical research, guidance of resource allocation and quality control. Having initially begun this research investigating the prediction of mortality outcomes in the paediatric intensive care unit (PICU) I have broadened my scope to patients outside of PICU, seeking to identify children early during their illnesses who are at risk of serious illness requiring PICU,” says Dr Pienaar.

The research up until now has been directed towards the identification of characteristics that are both unique to children with serious illness in South Africa, but also accessible to clinicians in settings where expertise and technical resources are limited.

Research still in the early changes

The research is still in its early stages but next year a series of expert review panels will be held to investigate the selection of variables for the model, after which the collection of clinical data will begin. Once the data has been collected and prepared, a number of candidate models will be developed and evaluated. This should be concluded by the end of 2022.

Says Dr Pienaar: “The need to engage with the rapid proliferation of technology, particularly in the realms of machine learning, mobile technology, automation and the Internet of Things is as great in medical research now as it is in any academic discipline.

“It is critical that research, particularly in South Africa, engage with this in order to take advantage of the opportunities offered and avoid the dangers that go paired with them. Together with the technology as such, it has been essential to pursue this project as an interdisciplinary undertaking involving clinicians, biostatisticians and computer engineers.”

Hope for the research  

Dr Pienaar says he was very fortunate and grateful to be the recipient of a generous interdisciplinary grant from the UFS which has allowed him to procure software and equipment that is critical to this project.

“The hope for this research is that the best performing of these models can be integrated with a mobile application that assists practitioners in a wide range of settings in the identification, treatment and early referral of children at high risk of severe illness. I would like to expand this research project to include other countries in Africa and South America and to use it as a bridge to collaboration with other clinical researchers in the Global South,” says Dr Pienaar.

As an early career researcher, Dr Pienaar hopes that this research can serve as a platform to build a body of research that uses the rapid technological advances of these times together with a wide range of collaborations with other disciplines in the pursuit of better child health.

He concludes by saying that he has had excellent support thus far from his supervisors, Prof Stephen Brown (Faculty of Health Sciences, UFS), Dr Nicolaas Luwes (Faculty of Computer Science and Engineering, Central University of Technology) and Dr Elizabeth George (Medical Research Council Clinical Trials Unit, University College London). I have also been supported by the Robert Frater Institute in the Faculty of Health Sciences.

News Archive

UFS study on cell development in top international science journal
2008-09-16

A study from the University of the Free State (UFS) on how the change in the packaging of DNA with cell development influenced the expression of genes, will be published in this week’s early edition of the prestigious international, peer-reviewed science journal, the Proceeding of the National Academy of Sciences of the USA (PNAS).

The PNAS journal has an impact factor of 10, which means that studies published in the journal are, on average, referred to by ten other scientific studies in a two year period. The South African Journal of Science, by comparison, has an impact factor of 0.7.

The UFS study, funded by the Wellcome Trust and the National Research Foundation (NRF), looked at how the change in the packaging of DNA with cell development influenced the expression of genes. It is very relevant to research on stem cells, an area of medicine that studies the possible use of undifferentiated cells to replace damaged tissue.

Prof. Hugh Patterton, of the Department of Microbial, Biochemical and Food Biotechnology at the UFS, who led the study, said: "We are extremely proud of this study. It was conceived in South Africa, it was performed in South Africa, the data were analysed in South Africa, and it was published from South Africa."

When a gene is expressed, the information encoded in the gene is used to manufacture a specific protein. In eukaryotes, which include humans, there is approximately 1m of DNA, containing the genes, in every cell. This length of DNA has to fit into a cell nucleus with a diameter of only about 10 micrometer. In order to fit the DNA into such a small volume, eukaryotic cells wrap their DNA onto successive protein balls, termed nucleosomes. Strings of nucleosomes, resembling a bead of pearls, is folded into a helix to form a chromatin fiber. The study from the UFS investigated how the binding of a specific protein, termed a linker histone, that binds to the length of DNA between nucleosomes, influenced the formation of the chromatin fiber and also the activity of genes.

"We found that the linker histone bound to chromatin in yeast, which we use as a model eukaryote, under conditions where virtually all the genes in the organism were inactive. It was widely believed that the binding of the linker histone caused the inactivation of genes. We studied the relationship between the amount of linker histone bound in the vicinity of each gene and the expression of that gene for all the genes in yeast, using genomic techniques. We made the surprising discovery that even through the linker histone preferentially bound to genes under conditions where the genes were shut off, this inactivation of genes was not caused by the binding of the linker histone and folding of the chromatin,” said Prof. Patterton.

He said: “Instead our data strongly suggested that the observed anti-correlation was due to the movement of enzymes along the DNA molecule, involved in processing the information in genes for the eventual manufacture of proteins. This movement of enzymes displaced the linker histones from the DNA. This finding now requires a rethink on aspects of how packaging of DNA influences gene activity."

Prof. Patterton said that his research group, using the Facility for Genomics and Proteomics as well as the Bioinformatics Node at the UFS, was currently busy with follow-up studies to understand how other proteins in nucleosomes affected the activities of genes, as well as with projects to understand how chemicals found in red wine and in green tea extended lifespan. "We are certainly having a marvelous time trying to understand the fundamental mechanisms of life, and the UFS is an exciting place to be if one was interested in studying life at the level of molecules," he said.


Media Release
Issued by: Lacea Loader
Assistant Director: Media Liaison
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl.stg@ufs.ac.za  
18 September 2008
 

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