New year's day is a time for reflection and I've been thinking about where I - and the field - has come from scientifically and what happens next.
I am very lucky in lots of ways, but in genomics I started lucky and young: in 1991, a lanky haired boy of 19, I taught myself to code to explore this new-fangled large scale database called "Expressed Sequence Tags" large scale (at that time) DNA database, now considered puny.
A postdoc in Rich Robert's group, Sanjay Kumar, gave me a copy of Kernighan and Ritchie programming in C, I got access to the VAX (!) machine at CSHL and then at ICRF in London and the venerable GCG software to develop my first program to compare profile HMMs to DNA directly
(this would go onto become "pairwise and searchwise" and this would then go to "genewise" - a protein homology gene prediction program which I am both proud and a bit concerned is still running in a variety of genome annotation programs)
In the late 90s I dived deeper into genomics and bioinformatics, having flirted with joining the City and working on options pricing, working with Richard Durbin at the Sanger Institute in the heyday of human genome "race".
When Celera (who also used my software, genewise) said they would beat the public project not because of data generation but because of their analysts, the Wellcome Trust, encouraged by John Sulston, doubled - quadrupled - down on analysis.
That in practice meant building a team around Tim Hubbard, Michele Clamp and myself, and I was talked into being the @emblebi side of the collaboration. We wanted a name that captured the EMBL side - discussed humEMBL and MumEMBL, but settled on Ensembl.
We worked like idiots; hired great people (many still on campus either @emblebi or @sangerinstitute - waves) and Ensembl's genes and proteins became steadily the bedrock for gene annotation, with friendly collaboration/competition with @GenomeBrowser on presentation.
Moving into the noughties I watched with interest the development of widespread cheap genomic polymorphisms - SNPs - and its promise for unlocking the genetics of common disease - and realised there were far too many very clever people in that field. I kept... a watching brief :)
So I dived again into an area with lots of clever people but less data scientists - genome regulation, chromatin modifications and what on earth was controlling the rather small number of protein coding genes in the human genome - the @ENCODE_NIH
Wrestling down complex genomewide experiments into something sensible and a crash course in histone / chromatin biology was brilliant fun, with a really great crew. Less fun was the blowback on the second consortium paper, but the data and many methods used today.
At the same time @emblebi was growing under Janet Thornton and the multi-talented @PaulFlicek (originally came as a "short 2 year postdoc") took on @ensembl and lead it to new heights. I entered a DNA-meets-protein partnership with Rolf Apweiler (sadly not on twitter)
Rolf and I aimed to coordinate and advocate for the services across @emblebi, supporting Janet in her push to make this provision of services a pan-European effort via @ELIXIREurope.
Looking back we did that and some, but only because of the excellent people @emblebi and across Europe in @ELIXIREurope. From 2005-2015 @emblebi provided the foundational resources for every type of biomolecular assay, allowing data to be shared worldwide for everyone's benefit
My own research always had a strong "practical algorithmic" bent - gene prediction, assembly, DNA compression and later still with @Nick_Goldman storing information in DNA (a great pub idea to Nature paper and patent story). But... I was getting research itchy.
I noticed the remarkable power of outbred association genetics in human disease (my watching brief), and "old school" pedigree, and then marker based, animal quantitative genetics from a happy stint on the Governing council of Roslin.
Why not do this for all biology I asked myself? Why do people only look at human disease as a phenotype? What are the limits? I realised quickly that although humans were a great species to study (and attracted lots of funding) there were a whole bunch of limitations.
At the end of my ENCODE time I had struck up a partnership with Jochen Wittbrodt - an endlessly positive and enthusiastic fish biologist - who near single handedly was pushing Medaka fish, the classic Japanese model organism, in Europe.
Medaka has a number of quirks. One is that the majority of transient transgenics distributed with low mosaicism in the embryo, making in vivo assays a one week not 3 months experiment (great for ENCODE). Another is that Medaka husbandry has a protocol for inbreeding from the wild
Over a hefeweizen I realised that using this we could make the same sort of resource people had made and used in Maize, Arabidopsis and making in Drosophila - a set of "wild" genotypes but inbred so one could replicate and change environment at will.
Almost 8 years later this idea is now bearing fruit in an @ERC_Research synergy grant with Jochen and we have developed, along with @Naruse_kiyoshi in Nagoya and Felix Loosli in KIT the first vertebrate wild inbred panel, the MIKK panel.
My research is now split between two outbred organisms - humans (they are great! in particular the @uk_biobank humans who have so selflessly provided data) and Medaka fish (also great!), with my long standing practical algorithmics focusing around @nanopore work
(throughout this time I've been a consultant for a variety of companies - some highlights: Compugen in Israel; then Solexa before they were bought out; then Oxford Nanopore - @nanopore - often being the academic foil /sounding board to the amazing @Clive_G_Brown )
In the middle of the 20-teens Rolf and I took over being Director of @emblebi from Janet Thornton, who now delights in her own research @emblebi and continues to do far too much for others (Vice President of Life Sciences for @ERC_Research).
@emblebi @ERC_Research This means advocating and coordinating across research and service delivery, and it was great to see @jomcentyre and @PaulFlicek be promoted to Associate Directors for @emblebi to oversee service delivery
The other pleasure for the last 5 years was to be on @GenomicsEngland board as a non-executive director, helping steer and challenge GeL in its delivery of genomic medicine in the UK.
Practical healthcare delivery is a complex, sometimes messy business, and I was the research/informatics voice on the board. I've been delighted to be involved in the planning of the Danish genomic medicine service, and the Swiss efforts (its complex and cantonal)
As someone who was at the start of the human genome sequence and annotation seeing it being used routinely in practice is .. quite a journey, but great to know it is making a difference to thousands of people - soon I suspect millions - worldwide
(this thread of mine leads my to my chairmanship of @GA4GH - the global standards organisation spanning healthcare and research in genomic data standards - another great crew I've been part of)
But ... what next?
One large topic - the Environment. The environment is about living things and is made from living things, and the price point of measuring the molecules in the environment - DNA, RNA, others - has dropped so much we have a new toolkit.
The health of the environment is key for the health and wellbeing of humans - both at micro and macro scale. Edith Heard, @embl's new Director General has a passion for this.
I am completely enthusiastic both strategically (eg, @ensembl's role in the Tree of Life project) and in my own research where the MIKK panel in Medaka fish allows exploring Gene/Environment interactions in a vertebrate in unprecedented detail and precision.
Another topic is the somewhat conceptually straightforward but practically fearsomely complex business of making genomic medicine work for Europe and the world. This is no ... small undertaking.
My role here is advoacy, advice and via the different trans-national organisations - @GA4GH, @ELIXIREurope and @embl realising the synergy about working together across the world to deliver better healthcare in this area. It's cheesy but no less true for this.
Some of this is real about practical delivery - rare disease genetics and infectious biology worldwide using genomics. Some still has annoying research components and mismatch between research and practice (I'd put a lot of cancer in this category).
Some is research in the transition to clinical practice. The blending in of genotype based risk scores in with clinical risk scores to impact population wide screening (for example, heart disease, colon cancer, breast cancer) is here.
A final big theme for the next decade I can see - Imaging. Imaging modalities have been completely transformed over the last decade, in particular cryo-EM (direct electron detectors) and super-resolution microscopy but in fact all across the board from wide-field to atomic scale
Imaging now is my go to phenotyping method of choice - with the amazing added ability to be able to use the time dimension as well as space (genomics has traditionally struggled on the time, with clunky experimental designs compared to the inherent time dimension in imaging)
Coupled with this, the rise of deep learning across the life sciences, but particularly in imaging gives a level of automation in the processing of imaging which just wasn't feasible 5 years ago. The future is super bright for imaging.
All these things - Environment, Medical Genomics and Imaging - I am sure will interact, but the general theme that biology will become - perhaps arguably is already - the leading data driven science will come true I think this decade.
Biology is so hideously complex - often near insanely complex for apparently the simplest of things - and yet so robust and reliable means the only way to study and understand it is to embrace this complexity with measurement, analysis and theory
I fully expect new surprising things to emerge as we progressively understand more and more how life works - ourselves as one instance of life, and ourselves as one part of this living planet. It's going to be ... fun.
As I said, I am a very lucky man. There are challenges ahead - in society, in the environment, in our planet, but nevertheless, I am looking forward to this decade.
