Focus on Dr. Mohammed El-Kebir
Author: Irati Hurtado
Dr. Mohammed El-Kebir was one of the recipients of the Greg Gulick Honorary Research Award in 2021, which provided him with $25,000 in Amazon Web Services (AWS) credits to study either cancer or COVID-19. His research in the field of computational biology has led to important contributions in the study of those two illnesses.
The project that El-Kebir proposed for the Greg Gulick Honorary Research Award focused on cancer phylogenies. Cancer originates through mutations that accumulate in a population of cells. There are different types of mutations: sometimes individual genomic bases are affected (single-nucleotide variants), whereas other times mutations affect large genomic regions (copy-number aberrations). Tracking these mutations and their evolution is important to design better cancer therapies for patients.
“So far, studies have focused on understanding tumor cells in bulk, which is not very precise,” El-Kebir says. His project aimed to “develop three algorithms that could help track tumor evolution at the single-cell level in order to get a clearer picture.”
The first algorithm was intended to identify single-nucleotide variants, the simplest type of cell mutation, using single-cell DNA-sequencing data. The second algorithm would build on the output from the first one and would output a phylogeny of the single-nucleotide variants. “You can think of this phylogeny as an evolutionary tree,” El-Kebir says. Lastly, the third algorithm would combine single-nucleotide variants and copy-number aberrations “to obtain a single comprehensive phylogeny.
El-Kebir’s project is still in progress. He wrote a manuscript on the first algorithm and submitted it to a journal, so he expects to have it published soon. In the meantime, he continues working on the development of the other two algorithms. He has been conducting research in other areas, also using part of the award funds. Thus, El-Kebir has also collaborated on other projects “trying to understand the phylogeny of coronaviruses.” Though these projects were not in his original proposal, he got approval to use the funds to conduct the research. In fact, El-Kebir co-authored a paper in the journal Molecular Biology and Evolution, which he also presented at the Annual International Conference on Research in Computational Molecular Biology.
Recently, El-Kebir had a paper accepted by RECOMB-CCB 2023, which was presented by PhD student Leah Weber. This paper focused on trying to infer the evolutionary history of tumors from single-cell DNA sequencing. Soon after, it was accepted to PLOS Computational Biology. Weber also presented this work at the NCI Spring School for Algorithmic Cancer Biology in Bethesda, Maryland in March 2023 and also at the Mathematical Methods in Cancer Biology, Evolution and Therapy in Banff, Canada this May. PhD student Leah Weber is also working on a second project “to infer B cell clonal lineages, which are helpful to researchers for the design of vaccines and developing effective immunization strategies as well as increasing our general understanding of the immune system.” While this publication is still in progress, she recently presented this work at RECOMB-SEQ 2023 in Istanbul, Turky in April.
Working with El-Kebir, Weber has experienced the benefits of the Greg Gulick Honorary Research Award. She says, “Overall, this award was helpful in providing computational resources to run numerous simulations simultaneously under a variety of conditions and parameters to ensure the robustness of our tumor phylogeny inference.”
Regarding the use of AWS to conduct the project, this was the first time El-Kebir actually used AWS. “The transition to AWS was very smooth,” El-Kebir says. The office of Research IT helped him get started and within days he was ready to use AWS all by himself. El-Kebir says that “there are also a lot of online resources and forums to learn about AWS if you get stuck with something.” Overall, El-Kebir thinks the process of using AWS was quite similar to using his own server, which he has employed for previous research projects. However, he also thinks that researchers considering the use of AWS “should become familiar with the different storage options and should keep their data separated from their code.”
In the future, El-Kebir plans to continue examining cancer evolution using computational methods. Although he continues using his local server as well, El-Kebir had a very positive experience with AWS. There are still many open questions in the field of cancer phylogenies and El-Kebir is ready to make some exciting contributions to the field.