Day 5 - Following the White Rabbit

This was written by Kent C. Brodie

Have you ever worked with a vendor support, and after much back and forth, ended up with an answer, "works for us, so it must be something with your setup, sorry!" This is such a story. And like most similar situations, I learned some good lessons worth sharing.

The Background (our environment)

I work in the Human & Molecular Genetics Center, a large center within a private medical school. We currently deal with whole genome analysis, and let me tell you, it's pretty fun. There's lots of data, lots of PhD-type people doing complicated analysis, lots of servers, and lots of tools. Did I mention there's lots of data?

The foundation of all of this is a Sun Grid Engine (SGE) cluster and a software package from Illumina, Inc, that does nifty genetic things like "demultiplexing", "alignment", "variant calling", and several other sexy scientist things The cluster isn't huge, but it's powerful enough to get the processing done in a reasonable amount of time, between 8 and 14 hours depending on the data.

Fast servers. Dedicated 10gb network. Industry-standard cluster software. What could go wrong?

The Problem

This clustered processing job was failling, but only sometimes. Specifically, the demultiplexing and variant calling steps always worked fine, but the alignment step did not. To make debugging harder, the process would run for 12 or 14 hours before blowing up.

In the resulting error log file, I found several instances of this kind of error:

AlignJob.e22203:error: commlib error: got read error (closing "baku/shepherd_ijs/1")

I also saw errors like this:

[2012-10-13 00:47:38]   [kiev.local]  ERROR: The ELAND extended file for the mate 2 reads 001_eland_extended.txt.oa) could not be found.
[2012-10-13 00:47:38]   [kiev.local]  qmake: *** [205P_GCCAAT_L001_001_pair.xml] Error 1

It's important to point out that the software worked just fine in all cases on a single node. It's just in the SGE environment that it failed. The Illumina pipeline is essentially really nothing more than a handful of binaries a few Makefiles. Many of you are familiar with "make" and its use - SGE introduces a new flavor of that called "qmake", which is like "make", but runs distributed when the code is designed to take advantage of it. In my case, "make" on a single node worked fine, "qmake" in the cluster did not.

Getting Some Help

The first place I turned to was, of course, Illumina, our sequencing equipment and software vendor. Because of the complicated nature of the setup, they really could not provide any clear answers. Their support responses were along the lines of "it's a cluster issue". "Contact your grid engine company", "It's a race condition, you probably have issues with your switches", and so on. They support their software tools completely, but can really only guarantee help in single-server installations. Due to the multiple variables in a typical cluster setup, Illumina cannot support customer-built clusters. (Illumina sells a specific cluster setup, but we do not have that).

I had a few leads from their support, but I was basically on my own.

And So It Begins

Being a bit new to the SGE environment, I figured I had probably missed something. There ARE several installation options to choose from, and so I went off to test each and every possible option.

When debugging a problem, most of us sysadmins dive in, execute a task, analyze the result, and repeat until the problem is solved. This is how I worked on this - no surprise there, but remember, I had to wait at LEAST 12 hours or more to even find out if my changes had any effect. Let me tell you, that's not fun. The emotional roller-coaster of THINKING I had solved the problem, only to find out the NEXT DAY that I had not, was incredibly difficult and took its toll.

Tick, tock, tick, tock.

I tried one change at a time, but in some cases, multiple changes – all depending on gut feeling and experience. The combinations of changes got pretty crazy. All of my attempts ended with frustration - no matter WHAT I did, I got the same errors. Here is the abbreviated list:

• Various versions and implementations of Grid Engine (official Oracle SGE, open source "Son of Grid Engine", and multiple versions of each)
• Various 10-gig switch settings (enable/disable STP/portfast, flow control, etc)
• Physical connections to the switches (all nodes on one switch vs multiple switches, etc)
• Grid engine options dealing with spooling (local? centralized? classic(flat) vs BerkeleyDB?)
• Number of actual processes per node when running the job

Finally, a Breakthrough

At this point, over a month has passed in this troubleshooting marathon. I am losing sleep. The boss is cranky. He wants to replace the cluster with several standalone 48-core machines to run the Illumina pipeline, which means he's lost faith I can ever solve this. (A horrible solution by the way, because even on a 48-core server, a single alignment job takes 40 hours.) It WORKS, but it takes 40 hours: four times longer than when clustered.

In my daily Google searches about grid engines and configurations and such, I eventually come across the default configuration for ROCKS clusters with SGE – and notice something I've not yet tried. (ROCKS is a software distribution to rapidly build physical and virtual clusters, pre-loaded with all sorts of goodies).

By default, SGE uses and internal RSH mechanism to make all of the connections to the other hosts and/or back to the grid master. But in the ROCKS distribution, SSH is used. Why SSH? Because for extremely large clusters OR for jobs that require a boatload of communication stream, RSH will run out of connections due because it only uses ports below 1024.

Lather, rinse, repeat. Wait 12 hours.

Bingo. Well, sort of. The "commlib" errors are now gone. Seems the commlib error was trying to tell me, "can't establish connection because there's no more ports left". I am now left with the missing file(s) error.

I am closer.

The situation seems simple - there are files that a job on a node out there is expecting to be there, and it isn't. OK, so the vendor's claim of some "race condition" seems possible. The testing continues.

Nothing. Nada. Zip.

Another 3 weeks pass. I have made zero progress on the final error - the famous missing file. I have even gone so far as to acquire a demo Force10 switch from my partner/reseller to try out to see if that solves the problem (Our cluster installation has a Dell 8024 10-gig switch, a choice made by a former manager. It was not on our storage vendor's approved-hardware list..). The new switch makes no difference. Despite that, I am extremely thankful to my reseller and Dell for allowing me to test the switch.

A pair of breakthroughs?

Finally, in week 8, two things come together, both pointing to issues with Illumina software and "qmake".

Use the Source, Luke

First, I find some interesting comments in two of the complicated Makefiles in Illumina's code. Due to licensing restrictions on the code, I cannot post the comments or code here, but the guts of it boil down to that (this is paraphrased), "due to the limitations of qmake ... we have to do it this way".

This is interesting. Even one of the authors of the code is sort of acknowledging that he or she has had issues with qmake – the core utility I'm using in SGE.

A funny thing happened on the way to the Forum

Second, at about the same time, I got an answer from an online forum for people doing sequencing analysis ("seqanswers"). As a hail Mary pass, I post specific questions about my issue, and from more than one person I hear back, "use distmake".

Distmake is an interesting animal. It's a distributed make. It's kind of like qmake, but it BEHAVES like "make" does on a single server. It's a little hard to explain, but the difference showed up in my logfiles. When I ran the alignment job using "qmake", the log was peppered with log entries from every node in the cluster. Node A did this step, node C did that step, and so on. With "distmake", every single log entry is from ONE node. The job distribution works behind the scenes, but it also works within the SGE framework. This is critical, since we depend on SGE for the scheduling of all of the jobs.

And.. it worked!

(Personal note, as soon as this happened, I took 2 days of vacation to celebrate and basically do NOTHING except clean my garage and catch up on my favorite tv shows).

What was wrong? Why this failed in our environment, but works ok "at Illumina", I can't say. The type and size of the data? The number of nodes in the cluster? The sequencing/alignment options? Endless possibilities. My own conclusion is that under many circumstances, the Illumina code and qmake, the heart of SGE, simply do not behave well together. I have had difficulty convincing the vendor of that, and have to settle for the fact that I have a working solution. A solution several other sites are using, by the way.

Lessons learned

I learned several lessons while going through this process. Some are technical tidbits specific to SGE, and some are more general advice. Some of these seem obvious now, but during those two months, it wasn't.

Sun Grid Engine lessons

• In my opinion, Son of Grid Engine is where it's at. It is a much more active project and gets quick bug fixes. Oracle DOES still support their own SGE product, but updates are slow, and I wouldn't bet long term banking on SGE support from them. It was, after all, a Sun product.
• SGE spooling: go with local spooling. And classic mode is just fine except for perhaps the largest (hundreds of nodes) clusters, that's the only time you probably really need BerkeleyDB.
• SGE ports: Despite what the documentation says, do not depend on scripts and such to define the ports used for qmaster or execd communication. Always, always, use /etc/services entries.
  
• SGE communication: Use SSH. ROCKS has it right. # SGE error messages blow chunks. Just sayin'.

Other Lessons

• Do your own troubleshooting: The most important thing I learned from this experience was that I let myself be led, accidentally, by a software vendor. Following only their suggestions had me distracted with red herrings for too much time. Without predetermined suggestions for what might be wrong, I may have uncovered the flawed code earlier.
• Problems with one process are not necessarily related. I initially thought the COMMLIB and MISSING FILE errors were related. They were not.
• There is a support forum for EVERYTHING: I can't explain why I didn't stumble upon SEQANSWERS earlier. I just missed it. I'm a sysadmin for a relative small community (institutions that do their own genetic sequencing), and I'm guessing the handful of us that are in this are WAY too busy to be real active on the Internet :-) . I guess I was looking for the wrong community (SGE users), when the proper community was there all along (sequencing analysis users). http://seqanswers.com/
• distmake is basic, but really cool.

I hope you enjoyed my little tale! Now go finish your Christmas shopping. There's only 19 shopping days left.

Further Reading

(Author note, if you do nothing else, at least watch the NOVA episode. It's awesome. Really)

• PBS Nova episode "Cracking your genetic code" - features, in-part, my boss, Dr. Howard Jacob.
• Main PBS "Cracking your Genetic Code" site, with many educational links (including one that shows you how to extract your own DNA!).
• Illumina, Inc: Manufacturer of the world's most widely used sequencers
• SEQanswers: A super-useful site for just about anything to do with genetic sequencing>
• ROCKS Clusters
• distmake