The Denisovan Dilemma: Examining Protein Evolution Between Denisovans and Humans
Background
This paper was a final project conducted for Computational Biology: Structure and Organization of Biomolecules and Cells, which focused heavily on computational protein biology, which is a realm that I'd never delved deeply into before this class. Ancient proteomics is an emerging field in paleobiology adjacent to the genomic work that I'm interested in, and this project gave me the opportunity to move down the central dogma of biology—from DNA to protein—and apply the methods of modern protein biology to biological material that is hundreds of thousands of years old. The difficulty of ethically obtaining ancient samples is a limiting factor for many student researchers interested in this field, so the chance to work computationally on material that I may work on in the future was incredibly rewarding.
While this piece could also have fit into the leaves portion of this portfolio, its emphasis on methods and its reliance on data aligned more closely with my classification of the stem section. I worked primarily on the phylogenetic analysis to understand how closely related the raw, linear sequences seemed and the generation of the proteins with a tool called AlphaFold, which has been a revolutionary tool in protein biology that can closely predict the structure of a protein from just its amino acid sequence. Additionally, I provided the archaeological context in the introduction and background.
Reflection
As mentioned above, this paper was my first attempt at applying the skills that I've developed in my coursework in biomedical computation contexts to a bioarchaeology dataset. While it was a small-scale study due to the computational limits of our group's laptops and minimal availability of sequences from Denisovan samples, I still learned a lot from the issues that came up, primarily in sequence quality, a circumstance that comes up in most molecular analyses of ancient samples. Being faced with this issue and figuring out how to deal with it will likely be a constant struggle, and through this project I've learned what to do, and, even more importantly, what not to do.
Getting the experience of writing a more technical piece synthesizing biological and archaeological concepts helped me build the important skill of communicating across disciplines, as we worked on making the paper accessible to people with expertise in computational biology, who don't know much about the Denisovans, and in archaeology who may not know about the methods that were used to generate the data and findings. It was also a lesson in learning how to create phylogenetic trees that are easily readable, as that has been an issue I've run into in the past reading papers. Placing an emphasis on color-coding and truncating the generated trees to only the portions that we wanted to draw attention to was difficult, but rewarding. I would love to have had more time to fiddle with the program I using, and try to use it in tandem with a graphics software to improve the legibility even more, and I hope that at some point in the future I can build on the skills this project taught me to do so!