Posted By: HGG Advances
Each month, the editors of Human Genetics and Genomics Advances interview an early-career researcher who has published work in the journal. This month we check in with Sofia Papadimitriou (@sofiapapadim) to discuss her paper “Toward reporting standards for the pathogenicity of variant combinations involved in multilocus/oligogenic diseases”.
HGGA: What motivated you to start working on this project?
SP: I always had an interest in the field of medical genetics, and oligogenic diseases specifically intrigue me because of their challenging nature, as even after years of research since their first official reporting in the early 1990s, our knowledge on the biological mechanisms underlying such diseases is limited and reaching a definitive genetic diagnosis is still difficult. In our lab we have been developing various computational tools using oligogenic disease data. On the side, two years ago, we started the tedious work of curating and assessing the quality of this data, in order to make sure that we are using accurate information for our tools. Our paper presents our findings from this work.
HGGA: What about this paper/project most excites you?
SP: With this paper we, for the first time, openly pinpoint the reporting and pathogenicity assessment issues found on scientific papers presenting oligogenic cases, and we provide some initial guidelines. Personally, I find this initiative important as oligogenic diseases have started to gain a lot of attention during the last years. Therefore, we should ensure that the data and conclusions presented are carefully and properly assessed and that there is enough evidence to accompany the pathogenicity claims for combinations of genetic variants leading to disease.
HGGA: What do you hope is the impact of this work for the human genetics community?
SP: I hope that our paper stirs a fruitful discussion in the scientific community on how to improve the quality of the reported oligogenic data and can offer a solid ground for the development of standardised guidelines that will be used and be required every time an oligogenic case is being reported. Data of good quality will ensure that patients with an oligogenic disease will be able to be consulted properly, receive an accurate genetic diagnosis, and that any findings can lead to effective personalised treatment options.
HGGA: What are some of the biggest challenges you’ve faced as a young scientist?
SP: As a young bioinformatician working in the medical genetics field, I realize how interdisciplinary the field actually is. In order to conduct well-grounded research, diverse skills are required: different computational skills from coding to software development, good knowledge and understanding of genetics, good knowledge of genome sequencing technologies and how genomic data are created, statistics, good communication skills, and the list goes on. Another important challenge for me is the realization that bias exists almost everywhere, something that, naively, I did not expect in the past. I find the challenge of creating unbiased computational tools very important, and this has made me and my team curate more carefully the data we are using and re-design our tools to omit as much bias (that we can find) as possible.
HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?
SP: In general, I am intrigued by paleogenomics. I find the emerging findings from DNA sequencing on fossils very fascinating, as we can now understand better not only the culture and quality of life thousands of years ago, but also study and re-think the way we understand evolution. For example, I recently read a study conducted on individuals who lived over the past 10,000 years, with the aim to understand the evolution of the immune system. The authors showed how our genome became enriched with advantageous gene mutations related to host-pathogen interactions after the start of the Bronze Age, something that they suggest is linked at the same time with a higher risk of inflammatory disorders in post-Neolithic Europeans.