Meet José María González Pérez-Silva from the Genebuild team! José describes his work at Ensembl, the experience he had during his university studies, and how he winds down when not surrounded by annotation data.

When did you join and what is your job in Ensembl?

I joined Ensembl in August 2021. Work from home was still in place, so I joined from Spain. It wasn’t until a couple of months later, in September, that I moved to the UK and finally joined the team on campus.

I’m a member of Ensembl Genebuild, so I work mostly on genome annotation. That involves not only running the annotation pipeline for any assembly of interest, but also some development. Specifically, we continuously try to improve the process of annotation either with state-of-the-art third-party softwares or with our own. The former implies keeping up-to-date with recent developments, while the latter requires more time from us but allows for more tailored approaches. Of course, as all of you know, no matter how optimised a pipeline is, it will always require some prompt debugging/patching to adapt to specific circumstances.

What do you enjoy about your job?

Mainly the fact that I get to work on my field of choice. I was introduced to genome annotation during my predoctoral studies and I fell in love instantly. To be able to make sense (as much as we currently can) of the code that defines a species would on its own be magical. But to know that others will build on top of this to further understand life really makes my day. At the end of the day, to annotate a genome is like being the first one to read a wonderful book. A book that took millions of years to be completed by adding, subtracting, and editing its content over generations to finally define a living organism and its relation with the environment. In that sense,being part of Genebuild is like having access to a library of first editions. What’s not to enjoy?

“Romantic” outburst aside, in a more pragmatic way, I really enjoy the variability of my projects and the freedom to (within reason) manage my own time. To be able to allocate a full afternoon to intensely focus on my machine learning coding, or to start the day with some relaxing debugging or gene-set reviewing are great ways of avoiding getting frustrated with a project. Although, sometimes this is unavoidable, it really helps to enjoy one’s tasks. Even the less pleasant ones.

What are you currently working on (e.g. any particular projects, datasets, species)?

Lots of exciting projects! On one hand, I have my annotations. Specifically, I’ve focused a lot on farm animals and Lepidoptera . I’m starting to focus more and more on farm animals, but I still run the occasional assembly from Darwin Tree of Life (DToL). Of course, that’s only part of it. I’m also working on developing new “pieces” for our pipeline. Namely, we are trying to train a machine learning model for prediction of coding potential for transcripts, in an attempt to improve the classification of these as ‘protein_coding’ or other biotypes such as ’pseudogenes’ or ‘sncRNA’. We are still at a very early stage, but it really looks promising. I’m really excited to see where it lands. Additionally, I’m trying to automate two steps we usually have to tackle manually for most annotations, that is the stable ID mapping of re-annotations, and the search and load of RefSeq annotation into other features databases. Maybe not as exciting as protein coding prediction, but definitely a much needed quality-of-life improvement.

How did you get into bioinformatics?

I always knew that life sciences was what I wanted to do. But that’s where it stopped. I never thought much on which part of this vast field I wanted to focus on, and the way my degree was organised didn’t help at all as it was very holistic and not specialisation-oriented. I loved what I was studying, but hated to study, so I hardly ever got the best grades. This had some impact on my career choices, as I got discouraged to pursue a future in molecular biology (the first field that sparked some real interest in me) due to my grades. I went instead with applied animal physiology, my close second in preference.

I joined a summer internship programme researching the effect of different substances in cornea electrochemistry, when I started having frequent chats with a colleague who had just finished college. On the topic of which subjects to pick next year, he strongly recommended me to go for ‘computational biology’. I followed his advice without much thinking, and the next thing I know, I’m being introduced to this wonderful and amazing world full of available data, ready to be queried. It really changed everything! I ended up spending much more time on this subject than any other I participated in every optional work possible; I started to learn how to code in my free time and sent my scripts to my professor as alternative solutions to the problems he was suggesting, who eventually recommended me for a PhD position at his lab – in the molecular biology department of my university of all places!

What did you do before joining Ensembl?

My first research position, if one can call it that, was as an undergrad. I managed to get an internship in the research department of Fernandez-Vega Ophthalmologic Clinic, where I studied the effect of different peptides (neurolysin and gastrin) on the electrochemical response of cornea nerve terminations of mice to cold and pain. It was both extremely gruesome and tiring, as each experiment lasted four hours of uninterrupted (not even bathroom breaks!), detailed, mechanical work. Not great as a first experience, but I got some nice results out of that, and before I could realise it I was starting (unofficially as I hadn’t graduated yet) my PhD studies in the molecular biology department at my university.

My research group’s topic was ageing and cancer. But my focus was slightly different from my lab-mates (most of which were “proper” wet lab biologists). While they worked on pathological ageing, cancer, or even autism spectrum disorder, I started to build what my boss jokingly called “Methuselah’s zoo”, meaning de-novo annotating genomes of animals with some longevity-related peculiarity: a long life expectancy (or lack thereof), extreme resistance to DNA damage, or even alleged immortality.

We used a more old-fashioned manual method for the annotations, so in the span of my thesis I couldn’t cover more than a handful of the list of species we highlighted. I started working on whales, helping out with the annotation of the bowhead whale (Balena mysticetus), annotating the degradome of sperm whales (Physeter macrocephalus), and some specific genes in other Cetacea for comparison’s sake. I also annotated the degradome of Lonesome George, last member of the Pinta’s Giant Galapagos, some years after its death (which added to the many complications that arise from this project). I also got to participate in many “minor” projects that never got to see the light of publication, such as comparing some extreme-resistant tardigrades, studying the oddity of enamelled fishes, developing websites, or playing with Venn diagrams generation. After my PhD defence, I got to extend my contract for some months to finish some active projects. One of these was related to SARS-CoV-2, and included the genetic study of specific populations in Spain with apparent different resistances to infection. The other one consisted on the annotation and comparison of two species of jellyfishes, the so called “immortal jellyfish” (Turritopsis dornii) and a close relative that lacks this “ability” (Turritopsis rubra).

What do you do when you are not working? 

I have a really long list of hobbies, so I have a lot of things to divide my free time into. So many indeed that I’m usually running short of time, so I usually end up using some of my sleeping time for hobbies. Thus, my caffeine addiction. I watch an embarrassing amount of shows and films, for instance. And by “watch” I generally mean “binge-watch” (not a big fan of the classical weekly-release). I have no filter, either, I’ll watch whatever non-horror. I quite enjoy reading as well, but I’m much more picky about this. I love fantasy (huge Prattchet, Tolkien and Sanderson fan, to name some), but I read science fiction, philosophy, science and, from time to time, historical fiction as well. I spend a good amount of my free time playing video games. Mostly with my friends but some on my own as well. Nintendo and PC are my weapons of choice. On a more artistic note I like writing (haikus mostly, and a couple of short stories), drawing (despite my lack of talent for it), and crocheting. I’m also trying to learn Welsh.

But if I had to pick only one thing to do in my free time (sort of desert island scenario), that would be tabletop roleplaying games (such as Dungeons & Dragons). For those not familiar with this, it is essentially a story being told by one player, the Game Master (GM), with the help of a set of rules. The rest of the players are characters, each in charge of making their own decisions and choices, with the consequences of them being calculated by the GM, thus advancing the story. It is simply the best. And it doesn’t fall behind in terms of time invested, at all. I love researching different rule systems, designing adventures, drawing maps, creating character concepts. And that’s only for the games I’m mastering! I’m lucky enough to share this hobby with most of my friends, so I get to have a couple of ongoing games to play as well.