The uncanny valley of multidisciplinary studies

This was inspired by a conversation with a colleague today who suggested the term, as well as a particularly thorny paper that has now been in review for going on two years, and has been reviewed by four journals (and one conference)- and of course the wonderful xkcd for the format. Ugh! Sometimes it really does feel like I’m a zombie. A multidisciplinary undead. Blarg.

Arrgh - I'm a zombie. Brains!

Arrgh – I’m a zombie. Brains!

Here’s a link to the Wikipedia entry on “uncanny valley“. It’s from robotics and it describes how robots make us feel increasingly uncomfortable, uncanny, as they get more and more human like. It’s not a completely appropriate analogy to link it to publishing computational biology studies, but I think it actually makes a lot of sense. From the reviewers’ point of view the methods, language, format, and sometimes even goals of a multidisciplinary paper become more and more foreign as they move further into the territory of the other field. If they are too far one way or another they won’t be seen by the other side’s reviewers. Of course, there are those reviewers who are completely familiar with the middle ground- we’ll call them zombie-lovers, who have no problems. But getting a review like that is an exception rather than the rule.

Goodbye to two good friends

(Note: this post isn’t nearly as sad as it might seem from the title or the introduction below)

Yesterday I lost two close friends. We had been friends for five years, though our relationships had extended a tumultuous 10 or so months before that. Given that we still have unfinished business I expect our friendships to straggle on a little longer. But really, it’s over. My friends have helped me grow in a number of important ways- become more mature, deal with different personalities, forced me to communicate more clearly and to take criticism in a constructive light. The friendships both challenged me in different ways and supported me through a fragile time in my life. I will miss both of these friends for some different reasons- and some of the same reasons.

Like many friendships they have ended because of what other people thought about them. A small number of people had comments on our friendship- some of the comments, upon reflection, were probably well-placed, others certainly were not. But that outside influence is what really broke us apart. I hope that we can become friends again in the future- but we both will have changed so much in the intervening time that we may well be unrecognizable to each other. Still it would be nice to continue this friendship.

Bye Bye

Farewell Systems Biology of Enteropathogens and Systems Virology Centers – you will be missed but not forgotten.

Here are a few mementos of our time together….

  1. Ansong C, Schrimpe-Rutledge AC, MitchellH, Chauhan S,Jones MB, Kim Y-M, McAteerK, Deatherage B, Dubois JL, Brewer HM, Frank BC, McDermottJE, Metz TO, Peterson SN, Motin VL, Adkins JN. A multi-omic systems approach to elucidating Yersinia virulence mechanisms.Molecular Biosystems 2012. In press.
  2. McDermott JE, Corley C, Rasmussen AL, Diamond DL, Katze MG, Waters KM: Using network analysis to identify therapeutic targets from global proteomics dataBMC systems biology 2012, 6:28.
  3. Yoon H, Ansong C, McDermott JE, Gritsenko M, Smith RD, Heffron F, Adkins JN: Systems analysis of multiple regulator perturbations allows discovery of virulence factors in SalmonellaBMC systems biology 2011, 5:100.
  4. Niemann GS, Brown RN, Gustin JK, Stufkens A, Shaikh-Kidwai AS, Li J, McDermott JE, Brewer HM, Schepmoes A, Smith RD et alDiscovery of novel secreted virulence factors from Salmonella enterica serovar Typhimurium by proteomic analysis of culture supernatantsInfect Immun 2011, 79(1):33-43.
  5. McDermott JE, Yoon H, Nakayasu ES, Metz TO, Hyduke DR, Kidwai AS, Palsson BO, Adkins JN, Heffron F: Technologies and approaches to elucidate and model the virulence program of salmonellaFront Microbiol 2011, 2:121.
  6. McDermott JE, Shankaran H, Eisfeld AJ, Belisle SE, Neumann G, Li C, McWeeney SK, Sabourin CL, Kawaoka Y, Katze MG et alConserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systemsBMC systems biology 2011, 5(1):190.
  7. McDermott JE, Corrigan A, Peterson E, Oehmen C, Niemann G, Cambronne ED, Sharp D, Adkins JN, Samudrala R, Heffron F: Computational prediction of type III and IV secreted effectors in gram-negative bacteriaInfect Immun 2011, 79(1):23-32.
  8. McDermott JE, Archuleta M, Thrall BD, Adkins JN, Waters KM: Controlling the response: predictive modeling of a highly central, pathogen-targeted core response module in macrophage activationPLoS ONE 2011, 6(2):e14673.
  9. Aderem A, Adkins JN, Ansong C, Galagan J, Kaiser S, Korth MJ, Law GL, McDermott JG, Proll SC, Rosenberger C et alA systems biology approach to infectious disease research: innovating the pathogen-host research paradigmMBio 2011, 2(1):e00325-00310.
  10. Buchko GW, Niemann G, Baker ES, Belov ME, Heffron F, Adkins JN, McDermott JE (2011). A multi-pronged search for a common structural motif in the secretion signal of Salmonella enterica serovar Typhimurium type III effector proteinsMolecular Biosystems. 6(12):2448-58.
  11. Lawrence PK, Kittichotirat W, Bumgarner RE, McDermott JE, Herndon DR, Knowles DP, Srikumaran S: Genome sequences of Mannheimia haemolytica serotype A2: ovine and bovine isolatesJ Bacteriol 2010, 192(4):1167-1168
  12. Yoon H, McDermott JE, Porwollik S, McClelland M, Heffron F: Coordinated regulation of virulence during systemic infection of Salmonella enterica serovar TyphimuriumPLoS Pathog 2009, 5(2):e1000306.
  13. *Taylor RC, Singhal M, Weller J, Khoshnevis S, Shi L, McDermott J: A network inference workflow applied to virulence-related processes in Salmonella typhimuriumAnnals of the New York Academy of Sciences 2009, 1158:143-158.
  14. *Shi L, Chowdhury SM, Smallwood HS, Yoon H, Mottaz-Brewer HM, Norbeck AD, McDermott JE, Clauss TRW, Heffron F, Smith RD, and Adkins JN. Proteomic Investigation of the Time Course Responses of RAW 264.7 Macrophages to Salmonella Infection. Infection and Immunity 2009, 77(8):3227-33.
  15. *Shi L, Ansong C, Smallwood H, Rommereim L, McDermott JE, Brewer HM, Norbeck AD, Taylor RC, Gustin JK, Heffron F, Smith RD, Adkins JN. Proteome of Salmonella Enterica Serotype Typhimurium Grown in a Low Mg/pH Medium. J Proteomics Bioinform. 2009; 2:388-397.
  16. *Samudrala R, Heffron F, McDermott JE: Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systemsPLoS Pathog 2009, 5(4):e1000375.
  17. *McDermott JE, Taylor RC, Yoon H, Heffron F: Bottlenecks and hubs in inferred networks are important for virulence in Salmonella typhimuriumJ Comput Biol 2009, 16(2):169-180.
  18. *Ansong C, Yoon H, Norbeck AD, Gustin JK, McDermott JE, Mottaz HM, Rue J, Adkins JN, Heffron F, Smith RD: Proteomics Analysis of the Causative Agent of Typhoid FeverJ Proteome Res 2008.

*these were really from slightly before our time- but I’ll count them there anyway

Leading a collaborative scientific paper: My tips on cat herding

Large collaborative research projects, centers, or consortia have a single goal: to be funded for another round. That’s completely cynical, but it is not so far off the truth. The point of these projects is to advance science by bringing together many different experts in many different areas to do more than what could be done in a single R01-size endeavor. If there are no project-wide collaborative papers that come out of this effort going to high-profile journals there will be nothing- or very little- to make the claim that the project was successful. Why not just fund 3-8 R01-sized project that can work in isolation and accomplish the same thing or more? So publications are important.

The second thing to understand is that there’s no such thing as a ‘group-written’ paper, in my experience. Not truly. Someone always needs to step forward and take ownership of the paper to drive things forward otherwise it’s dead in the water. Maybe it can be two people, maybe it can be more- I’ve never seen it happen. So someone needs to step forward and be chief cat herder. This is a thankless job, but if it results in a solid, collaborative manuscript it can be very satisfying. Not to mention the fact that you will (or very much SHOULD) have your name first in the author order.

Here’s my metaphor for spearheading such a monster, errrr… paper.

Imagine that you’ve gathered a painter, a sculptor who works in clay, a sculptor who works with metal, and a DJ in a room- actually in many cases they’re not even in the same room, they’re distributed around the country in their own studios. Around the room (or in their studios) you have a canvas and paint, a block of clay, a pile of metal, and a box of vinyl. Your job is to assemble a work of art that incorporates all those elements together, blends them where appropriate, and is clear about how the pieces all fit together. You have a limited time to accomplish this. Art critics will be visiting after you’re finished to evaluate your work. Go.

Here are my list of thoughts on how to approach this kind of problem.

  1. Don’t think of this as a collaborative paper. In all likelihood the actual driving of the paper will be done by one person, and that’s you. If you wait around for everyone to chime in, contribute, take ownership for their sections, you will never get anything done. If you aren’t the leader of the paper, but the leader isn’t leading it MAY be possible to just start the process and take leadership. This can be politically dangerous and really depends on the specifics of the project and collaborations, but it’s something to keep in mind. You could be a hero.
  2. Think of this as a collaborative paper. This is a collaborative effort. I realize that this is directly contradictory to my first point. However, it is very important that you don’t lose sight of the fact that you are not the expert in many areas of the paper that you have to put together. Make use of others’ expertise but try to put this in direct requests for input of well-defined portions.
  3. Have a basic understanding of each component. This is really important. Everyone has different expertise and you will not become an expert in a new area by writing a paper. Don’t try. But if there are things that you really are not familiar with that need to go into the paper brush up on them by reading (actually reading from start to finish) previous papers from the group or current review articles in the area. This will allow you to understand at least where the collaborator is coming from and what they can offer.
  4. Don’t overload collaborators with many outlines and drafts. This will only make your collaborators stop paying attention. Instead try to put out one or two outlines, with discussion (teleconference or in person) between. Also with the draft, work with individuals to get portions completed instead of doing everything in multiple rounds of drafts that are commented on by everyone.
  5. Choose a way of collaborating on writing and communicate it with contributors. If you use MS Word for drafts make sure everyone uses the “Tracking Changes” option turned on. Otherwise it’s a nightmare to figure out what parts have been changed. Part of your job will be to manually merge all these changes into a single document. This is a tremendous pain in the ass, but it allows you to evaluate all contributions and make decisions about what to include or how things should be worded. Google Docs seems to work well for producing drafts collaboratively, but at some point the draft should be moved to a single document for finalization.
  6. At the early stages include, don’t exclude. Welcome everyone’s input and suggestions. At some point it may be necessary to make hard decisions about directions of the paper and that may make people unhappy. That’s something you have to live with- but try to listen to the group about these decisions. If there are people with suggestions on more work to do (either experiments/analysis or writing) and their suggestions seem reasonable, make it clear that it’s up to them to carry through with the actual work and try to get a timeline from them for completion. If their piece is essential to the project make sure that you have a plan for extracting this from them- there’s probably a nicer way to put this, but that’s the idea.
  7. At the later stages don’t let newcomers (or others) distract from the plan. If they have really great suggestions, listen to them. If their suggestions seem to distract from the story you are telling fall back on the, “well that’s a great idea, why don’t you investigate that and we can include it if the reviewers request it”- that is, after submission and review.
  8. Have a strategy to create the story you’re going to tell. It can be very difficult to start on a paper cold, when there’s only been discussion about what should be done. A reasonable approach is to do some preliminary analysis yourself then take this to the larger group for input. Make it clear that this is only one possible path and that you’re just trying to promote discussion. Make sure you’re telling a story- this is actually what a scientific paper is about. Be flexible about what the story is. It has to be consistent with the data available- but you may choose to incorporate portions of the results and leave out others that do not help the story along. See also my post on how to write a scientific paper.
  9. Try to avoid redundant effort. Generally this isn’t an issue because everyone is an expert in different areas so the actual work shouldn’t be redundant. Sometimes data analysis needs to be defined to avoid redundancy. If there are large sections to be written (such as an Introduction) it’s better to break it into smaller bits for different people to work on and call this out in the outline or draft so people are clear on who’s doing what. Everyone can revise/comment on all sections toward the end and that’s easier to merge than two disparate documents that are trying to talk about the same thing.
  10. Navigate author order and authorship carefully. This is tremendously important for most people on the project. The critical positions to identify are first author and last author (for biology papers anyway). If you are leading the paper you should be first author, but always remember that for many journals you can specify two or even three ‘first’ authors. For this kind of paper that might be necessary. Don’t try to limit authorship too much. These kinds of papers will have lots of authors. But try to be consistent; if you accept suggestions from everyone’s groups wholesale, it can cause conflicts. Consider that one group might consider technicians who performed the work to be worthy of authorship. If you say OK to this the other groups may chime in with all their technicians, etc. Follow the rules of authorship that you feel comfortable with and believe are ethically consistent, but remember that many, many people may have made significant contributions to the paper. This can be one of the most politically treacherous portions of the paper- have fun!
  11. Find a champion. Identify a senior author who you can communicate with and who you believe will support your positions, or at least will listen to your positions. There may arise situations that require having someone with authority agreeing with you to get others to fall in line.

Finally, here’s an example of a large collaborative research paper that I’ve recently published. It didn’t turn out quite as grand as I’d hoped (what paper does?) but it’s still a nice example of integrating the input of many different groups. I am currently working on (leading) at least three more such papers that are in various stages of being completed.

McDermottJE, ShankaranH, EisfeldAJ, BelisleSE, NeumanG, LiC, McWeeneyS, SabourinC, KawaokaY, Katze MG, Waters KM. (2011). Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems. BMC Systems Biology. 5(1):190.