An index to the China series appears at the first post.
September 20, 2016
My second full day in Beijing was my first work day! I visited the Phoenix Center and the National Institute of Biological Sciences, both located in a biotechnology park to the northwest of Beijing. Chao Liu, who had arranged for my visit, drove graduate student Zhen-Lin Chen and me over to the site. Our drive, starting after 9AM, was in heavy traffic, and we spent nearly an hour on the road. Chao Liu explained that he had hoped to buy a gas-fueled vehicle, but he was unable to get a permit quickly enough. Instead, he purchased a car that was entirely electric. I began noticing that lane markings are an elusive concept for many drivers on the road in Beijing. Frequently one will see other cars sitting with a front wheel in each of two lanes, as though they are uncertain which one they prefer. In South Africa, I have become familiar with minibus taxis asserting their way into another lane by threatening to sideswipe the side of a car occupying the target lane. That trick is seen from many different kinds of cars in China. Everyone blasts their horns, almost merrily.
Our first stop was the Phoenix Center. I was surprised to see that its massive logo was visible from the highway next door! When we arrived, my accompanying graduate student signed me into the guest register. A large stair case at the back of the massive entry hall was designed after DNA’s double helix. I, of course, had to pose for a photo. Soon my host, Jing Yang (who completed his post-doctoral training in the Liebler Lab at Vanderbilt) had emerged, and he gave me a tour of the impressive facility.
The first floor of the main building is given over entirely to proteomics. The site has an impressive inventory of instruments, with a couple of AB SCIEX TripleTOFs, some triple quads, ion Traps, and Orbitraps. The back hallway has a treasure trove of the premium Thermo Orbitrap Fusion instruments. Jing reported that the site features more than twenty instruments. It certainly delivers on its reputation as a premier site for mass spectrometry.
The second floor is devoted to functional proteomics. The third is devoted to translational studies. The fourth, happily, revolves around bioinformatics. Graduate student Zhen-Lin Chen and I gazed at the server racks, full of 192 blade nodes connected by InfiniBand.
In no time, I had been ushered to an impressive conference room, with tables set in a U around the speaker’s podium. It was the type of room that offers a green laser pointer and a stand-mounted microphone, of course. I shook a few hands around the table and introduced myself. Zhen-Lin set up a tripod; he was serving as cameraman for the three talks I would be delivering in Beijing. I had decided to write a special talk for the group on the subject of “Adventures in Large-Scale Proteomics: Publishing in a Consortium.” This is a topic I have visited before in this blog. I talked about six roles that had proven critical in three working group papers I had produced for the National Cancer Institute CPTAC program:
- The champion and the sponsor
- In describing my repeatability paper, I talked about the critical role played by the “champion” leading a paper effort, who must persist when criticism comes or the effort to frame a manuscript may be wasted. The “sponsor,” in this case, was Dan Liebler, who ensured that my work on the paper was protected even though the writing effort took much longer than expected.
- The archivist and the enthusiast
- In the task of writing our quality control assessment of CPTAC Study 1, my colleague Xia Wang and I adopted a “skunkworks” mentality. We would find a way to tell an interesting evaluation of CPTAC Study 1 without convening a large committee for that purpose. I produced quality metrics with our new “IDFree” quality software, she analyzed those metric tables in a multivariate statistical framework, she interpreted those metrics in terms of outliers, batch effects, and variability contributions, and then I edited text to explain those concepts to analytical chemists. In this task, I contributed the fervent desire to publish a study that had otherwise been abandoned to the archives, and Xia contributed much-needed enthusiasm and skill to take on the challenges I could not. It was a winning formula.
- The lingerer and the questioner
- My most recent publication for CPTAC was an effort that spanned more than three years. The project began as an effort to lay a firm foundation for the later organ-specific cancer papers by CPTAC 2, but it was delayed by a variety of factors. The primary one resulted from the change in analytical methods that took place after the initial “platform validation” experiments to differentiate a luminal breast cancer patient-derived xenograft from a basal breast cancer patient-derived xenograft. It would have been somewhat awkward to have published on the robustness of cohort differentiation technologies used by CPTAC only to have them use an altogther different set of technologies for their final experiments! I used the “interstitial” set of experiments as my data set instead. My course was also shaped by a presentation of interim results at Natcher Conference Center in November of 2013, when Alexey Nesvizhskii offered a critical insight in his question after the talk: I must consider a peak area-based assessment of quantities for the label-free sets and not just the spectral count-based assessment. My group scrambled to add this feature to our IDPicker software in order to fulfill this need. I felt quite proud to be able to have this work accepted for a special issue on Large-Scale Computational Mass Spectrometry and Multi-Omics by the Journal of Proteome Research immediately after my move to South Africa!
I enjoyed my lunch with the Phoenix Center investigators afterward. They had great questions and contributions to share while we ate lunch in an executive cafeteria area in the complex. I felt positive about the future that group will shape for itself in the years to come! With that, we began our walk over to the National Institute for Biological Sciences. The hike took us past a lovely lake, draining in a pretty rock-filled cataract to a collecting pool. We encountered children performing exercises and chanting along with their two adult leaders. The lake is the center of the biotechnology complex, and there are concentric circles of businesses and institutions expanding out from it.
Meng-Qiu greeted me with a hug. We have been friends since our time together in the Yates Laboratory; I was a graduate student, and she was a post-doc. Her laboratory at NIBS is pretty interesting. A row of stereo dissection microscopes lined the wall next to the entrance. The offices and break rooms had their windowsills crowded with succulent plants, including jade plants and Christmas cacti. She offered me a chance to look at “fluorescent worms,” and of course I accepted. Her lab studies the aging process in C. elegans, and so they had labelled a particular protein with green fluorescent protein. I watched the worm furiously wriggling in a circle (due to the effects of a mutation it carries). Imaging has an immediacy and intimacy that is conspicuously absent from mass spectrometry, I think.
NIBS has invested carefully in mass spectrometry. Like many core labs, it has a set of older instruments that have never really made it to “surplus.” The AB SCIEX QSTAR XL had certainly seen better days, as is true for the LTQ and the Bruker Autoflex. The updated lab, however, featured a Q-Exactive instrument for the core. Meng-Qiu’s group has an excellent instrument roster, with two Q-Exactive-class instruments, an LTQ XL Orbitrap, and an older triple-quadrupole that they’ve allocated to another group’s use. In a third facility devoted to metabolomics, NIBS houses an Agilent QTOF 6540 and an Agilent triple-quadrupole with iFunnel. NIBS has just hired a new director for the metabolomics facility from an excellent metabolomics laboratory in California. Things are looking up!
Soon, we emerged in the seminar room for my talk. I was happy to see the room filled with graduate students. I spoke about my recent papers in the field of quality control for proteomics. I enjoyed getting expressively mathematical with the students, including the use of yoga to discuss the Pythagorean theorem and some fun with the “handshake problem,” asking how many distinct handshakes are possible in a room with n partiers. It was quite a lot of fun. The students asked good questions, and almost nobody fell asleep, despite the 4PM start for my talk.
With a successful workday behind us, six of us packed into cars to visit a local hotel, where we ate an expansive dinner of excessive yumminess.