There are occasions when as bioinformaticians we question what we are really doing; when we need to sit back and consider whether we should even pursue a given project! There are even times when the chosen technologies are enough to turn our stomachs and to give us the Screaming Heebie-jeebies.

I am presently eager to secure a collaboration with a remarkable clinical scientist who is doing some very elegant research. He has some beautiful study designs and a fabulous patient cohort. He also has a huge stack of data – but it is all SOLiD. Nothing quite dampens a genome biologist’s mood quite like the mention of SOLiD data. This is strange – we all know of the 2-base encoded challenges of ColorSpace data – these challenges must be apocryphal since who has actually recently processed any of the data?

When at MGRC we had a good look at making SOLiD a native part of the “One-Click” pipeline. The mapping statistics were pretty unconvincing at the time and the project died a quick and painless death – the provider of the test data did not get the rich characterisation of personal variants back and I remained on my Illumina high horse – “deep base space is all that we need for meaningful variant analysis”. I too am guilty of the propagation of the “SOLiD sucks” mindset.

So, a couple of years since we last poked at SOLiD data and I have an external disk crammed with lanes of XSQ formatted LifeTech ColourSpace data. An an additional element of competition – the team from LifeTech are also trying to compete with us for some of the action in this remarkable project. This means that application of the LifeTech LifeScope software is off-bounds as an “unvalidated” black box solution – I need to craft a solution myself.

Former colleagues at Novocraft certainly have mapping software (NovoAlignCS) should be capable of doing something with the data – but NovoAlign expects fasta sequences and accompanying quality files. Reading of posts on BioStar and SeqAnswers reveals more mystery and misinformation on ColorSpace data handling but a gem emerges from the rough in the form of NGS_plumbing. Written by Laurent Gautier (whom I’ve met at a couple of meetings over the last few years) this software contains some rather simple methods to convert XSQ files into something more tractable for current mapping software. While written in Python and creating a few bizarre dependencies this is easily installed on Linux (but not on OSX) and even in a VirtualBox bioinformatics virtual machine the NGS_plumbing method chews through the XSQ files at a prodigious rate to create files that may be of some utility within scientific progress.

I don’t like SOLiD data – I don’t like that the XSQ file is binary and requires HDF5-devel to even peek inside it. I really don’t like that the resulting fastq file is a load of .0123 – it’s just not what I am used to seeing. The challenge though is not quite as horrendous as the naysayers would have led me to believe. So far so good. Of course, the proof-of-the-pudding will depend on some of the mapping statistics and whether we can actually pull some meaningful genetic variants out of the collection!

I have been a Mac user since my first Powerbook was purchased back in 2004. I have loved that crazy combination of Powerpoint, Terminal and UNIXness that just works! There are times when the rest of the world just doesn’t appreciate the power of Apple computers and key pieces of software are written for Windows computers only!

I am still a British citizen and although expatriate for the last 14 years I have a duty to yearly file my Tax return. This is an exercise in futility – I have no savings in the UK and the shares that I foolishly purchased back in the last ’90s generate sufficiently tiny amounts of income (measured in pence) that the process is not really worth it. Rules are rules and although I check each year HM’s Taxman would like my paperwork prior to the end of January or I will be obliged to pay a whopping GBP 100 fine! Crazy! Luckily there is some great software out there in the form of TaxCalc 2012 that will collate my lack of income and foreign resident status and prepare the convincing argument that I am not liable for either fine or big taxation bill. This piece of software however still runs only on Windows. A glaring oversight that thousands of Apple users must be aware of.

To deal with this challenge I have dragged around an old Windows VAIO computer that I bought back in 2002 prior to my realisation that Apple was the way to go. It used to dual boot either Windows 2000 or an old version of Redhat. A lovely computer. Last night when I started out on the tax return challenge I plugged in computer – the battery charging light came on. But then it did not start. A slight whiff of fried electronics and no beep. No lights. No action! BUGGER!

I am in a hurry to file this tax return and it is a money losing exercise at the best of times. I don’t wish to buy a replacement Windows computer (Alexander has a PC but it is in a possibly flooded shipping container somewhere near the Brisbane rive and waiting to clear customs). How can I deal with this challenge?

1. Buy a PC anyhow and be done with it
2. CodeWeavers CrossOver – has been used by a number of people with earlier versions of the TaxCalc software
3. VirtualBox and an install of a Windows software image

These all seem like the simplest and cheapest solutions. There are evaluation versions of CrossOver available and it seems like a plausible way to head. To abbreviate a long story it all works perfectly apart from the required Network Connection – this means the upload to the HMRC cannot work = long and slow painful fail.

The next attempt was with VirtualBox – I discovered this link that provided some helpful suggestions as to how free Microsoft images could be used. It all sounded absolutely fabulous but again I could not coerce the Networking to function properly and could establish no external link beyond the virtual machine.

Finally I tried the evaluation version of Parallels and a not so completely licensed .iso image of Windows 2000. I will purchase Parallels in 12 days time – this is the most awesome piece of software that I have used in a while. The networking worked fine, the functionality was complete and the install only took a few minutes. IE5 does not gel with the slightly richer presentation tools from TaxCalc so with a minor upgrade to IE6 (I cannot believe that I am actually writing this) and the software was installed and my Tax return (prepared last night using network impaired CodeWeaver CrossOver functionality) was uploaded with almost 2 days of time to spare! = Hoorah….

I dislike filing tax returns, I dislike Windows and I dislike software that is bound to a single platform. CodeWeaver and Parallels have some amazing software that aims to reduce some of this pain and I am really impressed with both. The next step is to get the Illumina GenomeStudio software running on this OSX based laptop… <shudder>

The second of January already! The first day of salaried work in what is going to be an exciting and challenging year. As I spin up my RSS feeds after a couple of days of downtime we have just a plum genome paper from the boys at BGI and a collection of archael genomes published in PNAS – a quiet morning on the scientific digestion front.

Today also marked the delivery of the Christmas cards – thanks Biomax, MPOB, Felda and Eric for your thoughts during this festive season.

I had an enlightening discussion with a colleague this morning – she was voicing her concerns about the balance of career progression and personal interests and ambitions. What should one do when you wake up in the morning and work and career seem like an unpleasant hurdle? How can a passionate scientist trapped in a science-lite position acquire and mold the responsibilities that will provide the motivation and impetus to ensure satisfaction? This is a theme that I’ll try to work on over the coming weeks.

I would love to bring the Genome_S back to life immediately – I have a slight challenge in that the raw data and the server that the data resides on are currently in transit. This will remain an objective for the year and one that should be rolled into my own New Year’s Resolutions.

What about a full list of sensible New Year’s Resolutions for this genome biologist?

• Think fit = walk more and break out of sedentary habits. I am stoked by the whole Fitbit concept and eFitness is an ambition, goal and requirement.
• Family = endeavour to ensure an optimal balance between work and family-life. Let’s see how this can be aligned with Think fit? Kids on bikes and a walk in the evening?
• Bioinformatics skill development = a management position doesn’t necessarily keep key skills alive. This requires some proactivity; let’s try to write some tutorials on R and genome informatics.
• Genome_S – this is a personal genome project and really requires some personal input to making it something that has clarity, precision or even meaning. It’ll be a herculean effort, but can be combined with skill development above!
• Scientific writing – there are some manuscripts from the past that have died. The dead are perhaps only undead and with some delicious brains perhaps a couple of manuscripts can be revived? It is a long range goal but one that I must at least try!

I am completely rubbish at blogging! We started with a great fanfare in what would be the Northern hemisphere’s spring and have since crashed with very little to really show for it! As we roll into the final hours of 2012 I would like to take this time to evaluate whether this endeavour was such a spectacular failure and whether I should try to be a little more competent in 2013?

Yup – it was a failure on all fronts.

I can only talk about a little of what actually keeps me amused and busy during the corporate working day but the Prestome project shone brightly at the start of the year before stalling – personal human genome analysis is a complicated business. While the process of mapping reads to a reference genome is a computational exercise and the process of characterising CNV, LOH and genomic inversions is pretty routine it is the process of curating mutations and looking for the evidence of pathogenicity that is complicated and really without end! The Prestome case remains fascinating and it seems that a single genome sequence is not sufficient to make a meaningful call. It would be awesome to sequence an extended family, to perform RNA-Seq on muscle biopsy and to look at additional clinical chemistry parameters. This remains a challenge for the future and the man behind the Prestome remains a contact and someone who I am eager to meet in real life!

My other ambition for the blog was to openly explore my own genome – human_s. I purchased a shiny workstation, wrote some lovely code to present the data QC and then became distracted by other more pressing commercial engagements. I am sure that my own analysis would mirror what was discovered for the Prestome – a single genome can only tell me so much about myself and 2 lanes of data from 1.5 generation Illumina is probably not enough anyhow.

I am not one for dwelling on what has gone on in the past – let’s quickly move on into 2013 and have a spectacular year and try to improve on this blog’s rather lacklustre delivery. I know that there are some surprises in store for the new year – these will involve a number of changes, complications and challenges – but interesting times is where I wish to live. Watch this space and perhaps we can have a more coherent delivery of this bioinformatician’s view of what is hot and what is not?

Happy New Year to all – may your dreams and ambitions for 2013 all come true!

Finally the home genomics plan is coming together. When the shiny new Dell server was delivered, it didn’t quite reach my own threshold for perfection. I think that we are now at a level that I am happy to call perfect. I added an cheap graphics card and now have an ideal screen resolution on the monitor that I use – the embedded graphics have been disabled and will not be used again. The drive sleds from http://www.discountechnology.com arrived (on a Saturday no less = impressed) and the server is now populated with a few terabytes of usable disk space. The air-conditioner in the home office has even been refilled with refrigerant gasses so the room temperature can be better maintained when computing. The home network is now gigabit and while this doesn’t quite solve the USB 3.0 issues the ability to get data on and off the box is a little more streamlined.

Server complains at ambient temperature