We don’t use perl for everything, yes we use it for web data, yes we still use it as the glue language in a lot of cases, the most complex stuff is done with C (not even C++ as that is too slow). Others on site use Python, Java, Rust, Go, PHP, along with looking at using GPUs in cases where code can be highly parallelised
It is not just one application – but many, many applications… All with a common goal of understanding the human genome, and using it to assist in developing new understanding and techniques which can advance health care.
We are a very large sequencing centre (one of the largest in the world) – what I was pointing out is that you can’t just throw memory, CPUs, power at a problem – you have to think – how can I do what I need to do with the least resources. Rather than what resources can I throw at the problem.
Currently we are acting as the central repository for all COVID-19 sequencing in the UK, along with one of the largest “wet” labs sequencing data for it – and that is half the sequenced samples in the whole world. The UK is sequencing more COVID-19 genomes a day than most other countries have sequenced since the start of the pandemic in Feb/Mar. This has lead to us discovering a new more transmissible version of the virus, and it what part of the country the different strains are present – no other country in the world has the information, technology or infrastructure in place to achieve this.
But this is just a small part of the genomic sequencing we are looking at – we work on:
* other pathogens – e.g. Plasmodium (Malaria);
* cancer genomes (and how effective drugs are);
* are a major part of the Human Cell Atlas which is looking at how the expression of genes (in the simplest terms which ones are switched on and switched off) are different in different tissues;
* sequencing the genomes of other animals to understand their evolution;
* and looking at some other species in detail, to see what we can learn from them when they have defective genes;
Although all these are currently scaled back so that we can work relentlessly to support the medical teams and other researchers get on top of COVID-19.
What is interesting is that many of the developers we have on campus (well all wfh at the moment) are all (relatively) old as we learnt to develop code on machines with limited CPU and limited memory – so that things had to be efficient, had to be compact…. And that is as important now as it was 20 or 30 years ago – the data we handle is going up faster than Moore’s Law! Many of us have pride in doing things as efficiently as possible.
It took around 10 years to sequence and assemble the first human genome {well we are still tinkering with it and filling in the gaps} – now at the institute we can sequence and assemble around 400 human genomes in a day – to the same quality!
So most of our issues are due to the scale of the problems we face – e.g. the human genome has 3 billion base-pairs (A, C, G, Ts) , so normal solutions don’t scale to that (once many years ago we looked at setting up an Oracle database where there was at least 1 row for every base pair – recording all variants (think of them as spelling mistakes, for example a T rather than an A, or an extra letter inserted or deleted) for that base pair… The schema was set up – and then they realised it would take 12 months to load the data which we had then (which is probably less than a millionth of what we have now)!
Moving compute off site is a problem as the transfer of the level of data we have would cause a problem – you can’t easily move all the data to the compute – so you have to bring the compute to the data.
The site I worked on before I became a more general developer was doing that – and the code that was written 12-15 years ago is actually still going strong – it has seen a few changes over the year – many displays have had to be redeveloped as the scale of the data has got so big that even the summary pages we produced 10 years ago have to be summarised because they are so large.
From: Mithun Bhattacharya <mithnb@gmail.com>
Sent: 24 December 2020 00:06
To: mod_perl list <modperl@perl.apache.org>
Subject: Re: Confused about two development utils [EXT]
James would you be able to share more info about your setup ?
1. What exactly is your application doing which requires so much memory and CPU - is it something like gene splicing (no i don't know much about it beyond Jurassic Park :D )
2. Do you feel Perl was the best choice for whatever you are doing and if yes then why ? How much of your stuff is using mod_perl considering you mentioned not much is web related ?
3. What are the challenges you are currently facing with your implementation ?
On Wed, Dec 23, 2020 at 6:58 AM James Smith <js5@sanger.ac.uk<mailto:js5@sanger.ac.uk>> wrote:
Oh but memory is a problem – but not if you have just a small cluster of machines!
Our boxes are larger than that – but they all run virtual machine {only a small proportion web related} – machines/memory would rapidly become in our data centre - we run VMWARE [995 hosts] and openstack [10,000s of hosts] + a selection of large memory machines {measured in TBs of memory per machine }.
We would be looking at somewhere between 0.5 PB and 1 PB of memory – not just the price of buying that amount of memory - for many machines we need the fastest memory money can buy for the workload, but we would need a lot more CPUs then we currently have as we would need a larger amount of machines to have 64GB virtual machines {we would get 2 VMs per host. We currently have approx. 1-2000 CPUs running our hardware (last time I had a figure) – it would probably need to go to approximately 5-10,000!
It is not just the initial outlay but the environmental and financial cost of running that number of machines, and finding space to run them without putting the cooling costs through the roof!! That is without considering what additional constraints on storage having the extra machines may have (at the last count a year ago we had over 30 PBytes of storage on side – and a large amount of offsite backup.
We would also stretch the amount of power we can get from the national grid to power it all - we currently have 3 feeds from different part of the national grid (we are fortunately in position where this is possible) and the dedicated link we would need to add more power would be at least 50 miles long!
So - managing cores/memory is vitally important to us – moving to the cloud is an option we are looking at – but that is more than 4 times the price of our onsite set-up (with substantial discounts from AWS) and would require an upgrade of our existing link to the internet – which is currently 40Gbit of data (I think).
Currently we are analysing a very large amounts of data directly linked to the current major world problem – this is why the UK is currently being isolated as we have discovered and can track a new strain, in near real time – other countries have no ability to do this – we in a day can and do handle, sequence and analyse more samples than the whole of France has sequenced since February. We probably don’t have more of the new variant strain than in other areas of the world – it is just that we know we have because of the amount of sequencing and analysis that we in the UK have done.
From: Matthias Peng <pengmatthias@gmail.com<mailto:pengmatthias@gmail.com>>
Sent: 23 December 2020 12:02
To: mod_perl list <modperl@perl.apache.org<mailto:modperl@perl.apache.org>>
Subject: Re: Confused about two development utils [EXT]
Today memory is not serious problem, each of our server has 64GB memory.
Forgot to add - so our FCGI servers need a lot (and I mean a lot) more memory than the mod_perl servers to serve the same level of content (just in case memory blows up with FCGI backends)
-----Original Message-----
From: James Smith <js5@sanger.ac.uk<mailto:js5@sanger.ac.uk>>
Sent: 23 December 2020 11:34
To: André Warnier (tomcat/perl) <aw@ice-sa.com<mailto:aw@ice-sa.com>>; modperl@perl.apache.org<mailto:modperl@perl.apache.org>
Subject: RE: Confused about two development utils [EXT]
> This costs memory, and all the more since many perl modules are not thread-safe, so if you use them in your code, at this moment the only safe way to do it is to use the Apache httpd prefork model. This means that each Apache httpd child process has its own copy of the perl interpreter, which means that the memory used by this embedded perl interpreter has to be counted n times (as many times as there are Apache httpd child processes running at any one time).
This isn’t quite true - if you load modules before the process forks then they can cleverly share the same parts of memory. It is useful to be able to "pre-load" core functionality which is used across all functions {this is the case in Linux anyway}. It also speeds up child process generation as the modules are already in memory and converted to byte code.
One of the great advantages of mod_perl is Apache2::SizeLimit which can blow away large child process - and then if needed create new ones. This is not the case with some of the FCGI solutions as the individual processes can grow if there is a memory leak or a request that retrieves a large amount of content (even if not served), but perl can't give the memory back. So FCGI processes only get bigger and bigger and eventually blow up memory (or hit swap first)
--
The Wellcome Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2 [google.com]<
https://urldefense.proofpoint.com/v2/url?u=https-3A__www.google.com_maps_search_s-2B215-2BEuston-2BRoad-2C-2BLondon-2C-2BNW1-2B2-3Fentry-3Dgmail-26source-3Dg&d=DwMFaQ&c=D7ByGjS34AllFgecYw0iC6Zq7qlm8uclZFI0SqQnqBo&r=oH2yp0ge1ecj4oDX0XM7vQ&m=friR8ykiZ-NWYdX6SrbT_ogNXEVR-4ixdkrhy5khQjA&s=xU3F4xE2ugQuDWHZ4GtDn9mPBCKcJJOI0PYScsSNjSg&e=>BE.
--
The Wellcome Sanger Institute is operated by Genome Research
Limited, a charity registered in England with number 1021457 and a
company registered in England with number 2742969, whose registered
office is 215 Euston Road, London, NW1 2 [google.com]<
https://urldefense.proofpoint.com/v2/url?u=https-3A__www.google.com_maps_search_s-2B215-2BEuston-2BRoad-2C-2BLondon-2C-2BNW1-2B2-3Fentry-3Dgmail-26source-3Dg&d=DwMFaQ&c=D7ByGjS34AllFgecYw0iC6Zq7qlm8uclZFI0SqQnqBo&r=oH2yp0ge1ecj4oDX0XM7vQ&m=friR8ykiZ-NWYdX6SrbT_ogNXEVR-4ixdkrhy5khQjA&s=xU3F4xE2ugQuDWHZ4GtDn9mPBCKcJJOI0PYScsSNjSg&e=>BE.
-- The Wellcome Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.
--
The Wellcome Sanger Institute is operated by Genome Research
Limited, a charity registered in England with number 1021457 and a
company registered in England with number 2742969, whose registered
office is 215 Euston Road, London, NW1 2BE.