Tag: human microbiome

Well, I am writing this on my flight heading back from St. Louis after going to the “Human Microbiome Research Conference”

I have already posted some summaries of the meetings Day 1 and Day 2  and will soon do one about Day 3.  And you can find out more about the meeting from multiple other sources such as here, here, here and here.  But what I thought I would do here is give some of the story behind the meeting – why I went and what it was like behind the scenes, at least for me.  Note – I know this is very long – but hopefully it will give people a feel both for some of the science, some of the behind the scenes, and some of (my) history relating to this meeting.

Some prelude to the meeting

I headed out to the meeting from Davis on the afternoon on the Monday the 30th.  I was originally planning on only going to the meeting for the last day, Thursday. that was because, well, the 31st was my birthday, and I wanted to spend it with my family.  normally, I reserve important family events and do not travel or schedule things that conflict with them.  So, when George Weinstock invited me to give a talk at the meeting, I told him that I could probably only come for the last day.  So that is when he scheduled my talk.

But then as the meeting approached I changed my mind.  You see, in the last few months I have gotten more and more interested in the human microbiome as a research area.  I had done some work on the human microbiome.  For example, my lab was involved in a collaboration with Michael Zasloff at Georgetown University in which they were conducting human ileal transplants and we looked at the microbial recolonization of the ileum after transplantation.   This project was headed by a stellar student, Amber Hartman, who just finished her PhD in my lab.  Her paper was published recently in PNAS (which I note, we paid for the Open Access option there and really wish more people would do similarly).

Anyway, that project had been my main foray into human microbiome studies.  However, I have led or been involved in dozens of studies looking at the genomics of symbioses (good and bad) between animals and microbes (e.g., see these Open Access papers on Wolbachia, sharpshooter nutritional symbionts, deep sea worm epibionts, a cellulolytic symbiont of shipworms).  In fact, I have been moving more and more towards studies of communities of microbes that live in or on animals and plants.  And I have been writing on and off about the microbiome in my blog including the following posts:

• Metagenomics 2006
• A human microbiome program?
• More on the Human Microbiome Program Workshop – Day1
• Metagenomics 2007 Update
• NIH wants proposals on the human microbiome …
• Microbial Evolution and co-Adaptation: A Workshop in Honor of Joshua Lederberg – Institute of Medicine
• The human microbiome – term being used in many ways – but at least it is getting some press
• Posting Notes from NAS Microbes and Health Meeting here on my blog
• Overselling the microbiome award: Stephen Barrie on pre and probiotics at the Huffington Post
• More (you know you wanted it) on fecal transplants and the microbiome

And I guess as the meeting approached I realized I really do want to do more human associated studies.

Day 1, August 30, 2010: Getting there

So, given the above desire to go to the meeting, I changed my flight, and then headed on out on Tuesday PM.  As I was posting to twitter along the way and during the meeting, I am going to use my tweets to give some feel for what I was thinking as things were happening:

• phylogenomics Off to the human #microbiome meeting in St Louis – starting off by killing some microbeshttp://twitpic.com/2js01c

Tour de Lance

The trip getting there was OK … I got into Phoenix, my connection city and bumped into, of all people, Lance Price at the airport.  He had a cold, and I avoided him after a brief hello, and then got the good news that I was upgraded to first class. Imagine my surprise when who was in the seat next to me it the man with the cold, Lance Price.  This was funny in a way because I had been pondering a recent interaction I had with Price via my blog.  A while back I had written a post pointing to an interesting paper by Price on the penis microbiome and circumcision.  However, I was not completely happy with the paper, since the press release that came with it was quite misleading.  The press release had made some unfortunate statements that gave the impression that the study had direct implications for the transmission of HIV.  The paper had nothing directly to do with HIV – it was mostly a comparison of the microbes found on the penis of circumcised and uncircumcised males. Sure, this could in theory be connected to HIV since other studies had started to make connections between HIV transmission and circumcision and it was possible that the transmission differences were due in some way to microbiome differences.  But they did not show is in any way and it was inappropriate really to have any suggestion that their study was directly connected to the HIV-circumcision story.  So I said is in the blog and amazingly to me, Price, who happened to be the lead author, got the press release taken down and changed in a VERY short period of time.  Anyway, you can read more about that on my post.

So there he was, in the flesh, with a cold of some kind, sitting next to me.  It was actually quite entertaining …. We had a great time talking about penises and vaginas and anthrax and the FBI and all kinds of other nasty things (this makes me want to say – “and everything was fine until the flight attendant came over and had some paper in his hand, held it up and said” … but people might not get that if they have not heard of Alice’s Restaurant by Arlo Guthrie).  I am certain some of the others in first class were wondering WTF was wrong with us.

• Sat next to Lance Price on flight to #microbiome mtg – am still impressed w/ his response to blog of mine months ago http://ff.im/-pWTaU
• Passengers near me & Lance Price on way to #microbiome mtg got earful: anthrax, penises, vaginas, wounds, microbes everywhere

Stranded Landed in St. Louis

We landed around 11:30 PM local time and I asked a flight attendant what time zone we were in she said Eastern.  This meant that it would, be 8:30 PM at home.  So while taxiing I called my wife in the hope I could talk to my kids as they went to sleep to say good night.  But alas, it turns out St Louis is on Central Time and the kids were asleep.  We got off the plane and Price and I headed downstairs … He had checked a bag and after discussing it I decided to not wait and share a cab with Dr. Sniffly.  So I took a cab to the hotel. The hotel the meeting was at (and thankfully where my room was) was the Park Chase Hotel. It was perfectly nice, and my room was enormous.  There were some issues, like the proliferation of pillows on the beds, and the strange key card system in the elevators that did not work well, and the 12$ beers in the lobby bar, and the fact that they kept the conference rooms at something like 60°F but it was still an OK place to have a conference.

No food for you

Anyway, I checked in, dropped my stuff in my room and went out to try and find a place to eat.  On the way out of the hotel, I bumped into Ashlee Earl and Bruce Birren who were working on something on the computer in one of the common areas.  I would have lingered longer, since I have known Ashlee for many years as used to collaborate with her when she worked on one of my favorite organisms Deinococcus radiodurans in John Battista’s lab (see our paper on gene expression in Drad here). But since it seemed I was interrupting some important work, I headed out to look for food since I had missed dinner (note to self, getting upgraded on US Air is certainly better than coach but nothing special – no food except chips).

I headed into the streets to a place directed by the hotel front desk people.  Alas, even though they promised the place would be serving food at 12:10 am, it was not.  So I grabbed some simple thing at a cafe and then went to my room to crash, on what was now, my birthday.

Day 2: Start of the meeting

On the morning of the meeting start, I got up a bit late and rushed downstairs to the conference area.

• Well, I am late to the human microbiome conference this am – I hate meetings that start at 8 am, especially when not on west coast

I got my conference material and ID badge – I had missed the general introduction by George Weinstock and Jane Peterson and Larry Shapiro.  The current speaker was (I think) Jim Versalovic and I was standing in the way back trying to figure out whether to go get some coffee or get a seat.

The talk ended and then I saw that Bruce Birren was up.  Well, as Bruce does some good/interesting stuff and as I had seen him working away earlier that AM, I figured I should stay.  So I grabbed a seat in the way back, and got out my iPad to start tweeting.  I saw that some others were tweeting the meeting and had settled upon a hashtag of #HMP2010, so I started firing away.  I note I like to live tweet meetings for a variety of reasons, including that I think it is a good way to let people have a feel for a meeting as it is happening.  But I also do it to take notes and force myself to pay attention.

Alas, sometimes you do not always write things out perfectly.  Here are my tweets from his talk:

• Well, I made it … To catch Bruce Birren from Broad starting his talk on 16s surveys and developing high throughput approaches 
• The human microbiome meeting #HMP2010 is quite packed – microbes rule http://twitpic.com/2jynzt
• Bruce Birren says that they developed a 454 rRNA sequencing pipeline that has been tested & is accurate across centers; #HMP2010
• Birren used a mock community to test rRNA PCR methods – wonder if he has read our mock metagenomics paper http://bit.ly/cPaIKF #HMP2010
• Bruce Birren testing diversity estimators from rRNA PCR – for simulation got many more OTUs back than they put in #HMP2010 #sequencingerror
• Birren – given that they trust their PCR, now comparing many human samples – seems like they are way behind the field here #hmp2010
• Birren presenting clustering of samples based on rRNA analysis – but could do much better referencing prior lit on this #HMP2010
• Interesting question after Birren’s talk re: archiving samples & informed consent – key things to think about in this type of work #HMP2010

Anyway, more later about the mini firestorm that my tweets about his talk created.  I was moving on to other things at the time.  Like responding to my brother’s Michael’s Happy Birthday wishes, which he surprisingly sent through twitter, which he rarely uses.

Next up speaking was Ian Lipkin.  Lipkin is another one of the people at the meeting I first interacted with through my blog, though with him it was a bit more awkward than with Lance Price.  A few years ago now I had written a post about a paper from Lipkin on colony collapse disorder (CCD).  The post I wrote was not positive, let’s put it that way.  And one of the coauthors of the paper, wrote to me and basically told me I was a jackass and I was wrong about what I had written in the post.

Alas, they were right.  And so I did what I thought any good scientist would do if they published something that was wrong – I retracted the blog post and put out an apology (this will be a recurring theme here) and gave myself a new “genomic jerk award”.  Plus I wrote a new post discussing their paper.   And then I was stunned – Lipkin called me up to thank me for apologizing and retracting the post.  Since then I have interacted with Lipkin on and off over the years and have followed his work with some fascination as in a way he is an old school microbe hunter.

Anyway, here is what I wrote during his talk:

• Ian Lipkin now up discussing microbe hunting in the 21st century #HMP2010 – mentions problems with Koch’s postulates at start
• Ian Lipkin talking about emerging infectious diseases – says we have only scratched surface of sampling viral diversity #HMP2010
• Lipkin showing world wide air traffic to scare us (rightly so) about how fast EIDs can spread #HMP2010
• Ian Lipkin referring to Edgar Allen Poe and cryptography in trying to sort through Metagenomic data#HMP2010 #binningishard
• Lipkin talking about nothing controversial: autism and MMR and microbes #HMP2010
• Lipkin has looked at microbial diversity in biopsies of people w/ &; w/o autism – found microbes associated w/ autism #hmp2010
• apoorva_nyc asked: @phylogenomics what sort of microbes? that’s all this field needs, more gut/autism theories
• I wrote back: @apoorva_nyc he simply said that there are differences in the microbial diversity in patients with autism – not claiming causal
• Really like how Lipkin caveated his autism work by saying “this is one study in one place” & then asked for others to test if real #HMP2010
• Ok Ian Lipkin has won me over forever . He just quoted Yogi Berra and Neils Bohr in one sentence #HMP2010

Coffee with a Tiger

In the first break, I headed out to get coffee, as I was starting to drag.  I bumped into none other than Owen White, who also was going to get coffee.  Owen was one of the people who helped convince me to take a faculty job at TIGR in 1998.  He was the PI on the project to sequence the genome of Deinococcus radiodurans, the most radiation resistant organism known, and I was at the time working on the evolution of DNA repair and radiation resistance.  One of my first projects at TIGR involved helping Owen analyze the Deinococcus genome and write a paper on our analysis.  I note, look at the figures in that and other TIGR genome papers very very carefully and you will see some secrets Owen, I and others put in there.  For example, in the Deinococcus paper, search for “strangelove.”

I worked at TIGR for eight years before moving to Davis in 2005 and Owen and I worked together on many many projects.  Owen and I did not always see eye to eye on various things while I was at TIGR but I both respect his work enormously and still consider him a friend so it was great to see him from my point of view.

We went to the hotel cafe and got there just before all the others from the meeting since we snuck out just as questions were starting for the last talk.  And then we wandered back to the mixing area outside where the talks were and I bumped into an array of people I knew.  The meeting really was a “who’s who” of microbial genomics and human microbial studies including many of my old TIGR colleagues (most of whom were ow at either UMD or the J. Craig Venter Institute – JCVI).

More talks

Talks started up again I went back to my live tweeting.  I note, it was also interesting to see who else was tweeting the meeting and eventually to meet them in the flesh.  After the break there were four talks:

• Roger Lasken & Johannes Goll discussed metagenomic projects at the J. Craig Venter Institute.  They did a tag team talk with Roger focusing on whole genome amplification (which he was one of the pioneers of) and Johannes discussing the JCVI metagenomic analysis tools.  Here is what I wrote:
• Roger Lasken from the J Craig Venter Institute now talking about whole genome amplification w/ MDA to get at uncultured organisms’ #hmp2010
• Roger Lasken: phylogenetic analysis can help assess MDA samples – note work done by Jonathan Badger who used to work in my lab #HMP2010
• Johannes Goll discussing Metarep – JCVI metagenomics analysis tool #HMP2010 – now available / published http://ff.im/-pYRF7
• Lasken: shallow 454 sequencing with barcoding – 50-100 MDA reactions to verify 16S classification of HMP samples #HMP2010
• Best place to find out about Human Microbiome Project?: probably The HMP DACC #HMP2010 #somecoolthingshttp://ff.im/-pYTFo
• For software geeks: The MetaREP software is open source & uses CAKEPHP, Solr, MySQL mix to do rapid indexing and searching #HMP2010
• Makedonka Mitreva from Wash. U. then discussed various microbiome projects going on there.
• Makedonka Mitreva from Wash U Genome Center: shotgun metagenomics of 54 people x 5 body sites: oral, skin, gut, vagina, nasal #HMP2010
• Mitreva – the big problem in analyzing human microbiome metagenomics data is computational time –#HMP2010 #weneedbettermethods
• Ugh: Mitreva referred to “lower eukaryotes” – maybe she says this because the podium is high above the meeting hall? #HMP2010
• Mitreva: current tools for analyzing metagenomic data mostly die (my word, not hers) when analyzing massive new data sets #HMP2010
• Owen Whitethen gave an overview of the Human Microbiome Project Data Analysis and Coordination Center, which he runs. His talk was quite good – a good mix of detail about what they are doing and big picture commentary about the state and future of this type of activity.
• Next up Owen White on the HMP Data Analysis and Coordination Center that he runs #HMP2010http://www.hmpdacc.org/
• White: one of their goals is to have a nice, easy to use website to coordinate information about HMP #HMP2010see http://www.hmpdacc.org/
• White: major goal is to provide ease of access to certain types of HMP data #HMP2010
• Key issue: open data is important but ease of access and use of open data also critical #HMP2010
• Best place to find out about past & ongoing microbial genome projects?: definitelyhttp://www.genomesonline.org/ #HMP2010
• I almost said same thing: RT @mikethemadbiol#HMP2010 *I* care if we sequence another E. coli genome 😉 Though metadata ARE critical
• Key issue: genome and metagenome data is not very useful without metadata about samples, methods, etc#HMP2010
• White: some challenges in downloading data from short read archive from NCBI #HMP2010
• White: DACC putting together virtual machines to run all sorts of microbiome/metagenomic analyses – can run locally or on cloud #HMP2010
• White: his goal is to teach community to fish not give them food (i.e., to give community tools, rather than run things for them) #HMP2010
• Eric Alm gave the final talk in the session.  His was not about human microbiome work but instead about population genomics of Vibrio strains.   
• And now for something completely different but very
  relevant: ocean microbes and genome evolution from Eric Alm#HMP2010
• Eric Alm discussing Fred Cohan’s ecotype model for species formation in bacteria and archaea #HMP2010
• Eric Alm describing how microbial samples are collected from ocean water; me: informatics people need to understand these things #HMP2010
• Alm: comparing 75 genomes of strains of Vibrio species; note all of these are in essence same OTU/species but lots of differences #HMP2010
• A questioner asked about something relating to “higher primates” – come one everyone – stop the evolution bogusness #HMP2010
• Alm, in response to my question, says that much of their evolution analyses done on incomplete genomes but he thinks it works fine #HMP2010

Lunch and PM talk burnout

And then it was time for the herd of scientific sheep to go to lunch.  The mechanisms for getting up to the 11th floor for lunch were awkward. Two-three elevators, no stairs, and nobody sure exactly where to go. But people made it on up to a freezing cold room on the top with a nice view of the park nearby the hotel.  I had a relatively quick lunch, went outside on the balcony to get some air, and then it was time for the PM sessions.

I was now a bit burned out. Too many talks I think.  And it is a bit hard to tweet all the talks and not just space out for a while.  But I soldiered through, and tweeted some more,

Much of the PM talks are a bit blurry to me now, but here is what I wrote on twitter:

• Ruth Farrell & Richard Sharp, both bioethicists from the Cleveland Clinic talked about ELSI issues in the human microbome project
• Oops … Missed the first part of the talk on ELSI issues associated with the human microbiome project#HMP2010 #importantstuff
• Issues relating to microbiome ethics: genetic discrimination, GMOS, release of probiotics to world, gene therapy #HMP2010
• Richard Sharp discussing how patients seem willing to use GMO probiotics even if they don’t like GMO foods#HMP2010
• Sharp: patients may be susceptible to aggressive marketing of probiotics #HMP2010
• Sharp saying that we should not oversell the microbiome project – he should read my bloghttp://bit.ly/ahXB4n #HMP2010
• Jo Handelsman discussed some of her work on looking for antibiotic resistance encoding genes in microbes in the environment
• Jo Handelsman, one of my favorite scientists, now up talking about finding antibiotic resistance genes in the environment #HMP2010
• Jo Handelsman refers to the “resistome” – collection of antibiotic resistance genes in a community;#badomics word? – probably #HMP2010
•  I note, Jo Handelsman coined the word metagenomics many years ago #HMP2010 – this omics word seems OK to me
• Vincent Denef discussed population genomics in the human microbiome
• Vincent Denef from Jill Banfield’s lab discussing “how deep does the rabbit hole really go?” #HMP2010
• Denef now explaining his talk title – lots of closely related organisms and may have to distinguish at very fine scale #HMP2010
• Denef now giving homage to the red pill blue pill choice from the Matrix #HMP2010#Toldyoumetagenomicswascool #geekytoo
• Denef discussing metagenomic studies of preterm infant gut -using similar methods as in acid mine drainage studies #HMP2010
• Denef – looking at population shifts over time using metagenomics -getting to correlating pop. changes with specific allelic diffs #HMP2010
•  Denef showing how proteomics can be used in environmental studies – Banfield lab does v. cool stuff in this area #HMP2010
• A main worry re: metagenomic studies: like GWAS, lots of genetic variation but w/ few variables, will always find correlations #HMP2010

In the next break I bumped into Ian Lipkin and we agreed to go to dinner together.  Then the next session seemed to begin way too fast but it was good.

• David Relman was up first.  I note, before I got accepted to graduate school I had an offer to work in Relman’s lab on rRNA PCR studies (I do not think we ever met, but I am not sure anymore).  I wonder how my career would have ended up if I had joined his lab then …           
• David Relman is w/o a doubt the Philosopher of the Microbiome – always discussing deep questions #HMP2010
• David Relman discussing single cell genomics and other approaches to studying single cells in communities#HMP2010
• Relman: reagents in molec. biology freq. contaminated w/ DNA; this impacts many amplification studies when DNA levels low; #HMP2010   
• Margaret-McFall-Ngai who I have interacted with on and off over the years and love her approach to studies of symbioses.
• Margaret McFall-Ngai : vertebrates are a very old group & likely been associated w/ microbes for hundreds of millions of yes #HMP2010
• McFall-Ngai: humans are not the pinnacle/crown of evolution; me: just YAV (yet another vertebrate) #HMP2010
• RT @TheGenomeCenter McFall-Ngai: most human genes are old; most genes associated with human disease are also old#HMP2010 
• McFall-Ngai’s talk is so far an homage to model organisms and how they will be relevant to human microbiome studies #HMP2010
• McFall-Ngai encouraging everyone to study circadian rhythms of host-symbiont interactions #HMP2010
• Mihai Pop who I used to work with when we were both at TIGR.  He discussed metagenomic assembly methods.
• Mihai Pop says his talk on Metagenomic assembly will be very short b/c it is impossible #HMP2010
• Alas Pop didn’t end his talk, says one can make (somewhat) useful assemblies from metagenomic data; utility depends on goals #HMP2010
• Pop showing challenge in assembly by showing assembly of A Tale of Two Cities; repeats Ike “it was the” can confuse things #HMP2010
• Pop: genome assembly is hard b/c of 1) repeats 2) low coverage 3) sequencing errors – gets even harder for metagenomics #HMP2010

A bloggable dinner?

After the last talk that PM I got a drink in the bar and was hanging out talking to people when I realized I was late to meet Ian and I headed over to the lobby and off we went.  We found a place and sat down outside – good to not be in a freezing cold room for a while.  Mike the Mad Biologist of ScienceBlogs wandered by and we invited him to join us (not sure if his real name is public knowledge so not posting it here).  We had a good dinner and Lipkin even got the restaurant to bring out a candle for my birthday after dinner.

Drinks and criticism and bedtime stories

Afterward, we went back to the hotel,  I dropped off my stuff and headed down to the bar to get a birthday drink, and bumped into a crowd of people from the Broad, JCVI and UMD coming from a dinner they had for the sequencing centers involved in the HMP.  I skipped out for a fun 30 minutes to tell bedtime stories to my kids over the phone (I really wonder what the hotel staff lurking nearby thought while listening to me tell a crazy invented story about submarines, polar bearskin, whales, and strange activities).

Anyway I returned to the bar, got some complaints from the Broad and JCVI people about something I tweeted about Bruce Birren’s talk and then went to my room. The comments about my tweet led me to relook at what I had written and especially in light of having been thinking about the Lipkin blog retraction.  So after fretting a bit, I decided I probably was a bit over the top in some of my comments on his talk.  So I wrote up a mini apology and clarification on my blog at night when I wrote up notes on day 1.  In summary what I said in that post I quote here, in part to make this a very very long post, but also b/c I think it is relevant:

As I have tweeted many meetings I guess I am used to various aspects of such activities but many out there clearly are not.  Live tweeting a meeting is a rough thing in many ways, at least for me.  I want to give people a feel for the meeting, as it happens.  I want them to know what I actually think about talks, at least within some reasonable limits.  But alas sometimes, hopefully not too often, I get things wrong.  And sometimes I post something obnoxious.  And sometimes I miss key points.  To me, this is analogous to the conversations people have about talks all the time.  Overall, I think mostly I do an OK job tweeting meetings.  But occasionally I write something that does not sit right with others or myself.  And alas, today has one such tweet (well, only one I know of right now).

It happened during Brice Birren’s talk.  Birren, from the Broad, was discussing a few different things including studies done by the Broad in which they have tried to compare and contrast and use rRNA PCR studies done at different centers associated with the HMP.  Much of what he was discussing was technical details of the control experiments they did to assess how variable the results were between centers.  I felt at the time that he was placing this work in enough of the context of other rRNA studies of the human microbiome.  And I tweeted this feeling.

• phylogenomics Birren presenting clustering of samples based on rRNA analysis – but could do much better referencing prior lit on this #HMP2010
• phylogenomics  Birren – given that they trust their PCR, now comparing many human samples – seems like they are way behind the field here #hmp2010

But in the end, after discussions at the bar later, I think I may have missed the point of his talk.   I thought at the time that he was discussing solely new findings and new analysis tools that they developed.  To me, I did not like that he did not spend much time discussing other analysis tools nor how their work compared to other studies of the human microbome.  And that gnawed at me.

But in retrospect, I think perhaps he was focusing more specifically on the comparison across the centers.   In that context, the way he laid out his talk and what other work he referenced makes more sense.  I think perhaps he could have still placed things in a broader context but my comments in retrospect were a bit over the top and unnecessary.  As I said above, I think it is useful to try and post what I am actually thinking at the time.  I try to filter this if I know what I am thinking is rude, biased, obnoxious, etc; but I do post critiques if they seem relevant.  But my filtering was a bit off here.  Alas, now Bruce (if he reads twitter) probably wants to dump a beer on my head and people from Broad think I am a putz (well, some may have thought that before). I guess I may have to change the tuning on my filter a bit … but I still will try and post what I think at the time.  It is a fine balance I do not always do precisely … off to sleep and in the AM – Day 2 plus time to make some in person apologies …

In the end, I accept that live tweeting is a bit risky in the way I do it, where I try to not just say what people are saying but try to say what i think about what they are saying.  Sometimes my comments are overreactions or rude or wrong.  But I always try to correct them or clarify when something was off.  From the emails and tweets out there I know a lot of people follow along when I am tweeting a meeting and they seem to like it … Just got to try and be careful to not be over the top.

Other notes on Day 1 on the meeting.

In addition to my comments about the Birren tweet, I thought it might be of interest to post here what else I said about Day 1.

Well, Day 1 of the Human Microbiome Project meeting is over.  And overall, I think it was quite good.  So now for a Day 1 wrap up.

First, a bit about the meeting.  The meeting is formally called the “Human Microbiome Research Conference” and more information about it can be found here. It is directly tied to the NIH “Human Microbiome Project“, also known as the HMP, which has been in operation for a few years now.  The HMP is one of a small number of NIH “Roadmap” initiatives (these are also known as NIH Common Fund Projects).  These are cross cutting projects that are funded outside of the normal NIH departments/centers.  The HMP started a few years ago and is focused on studies of the communities of microbes that live in and on humans.  The HMP has so far funded a wide array of projects including some big scale and some smaller scale.  This meeting is I think the first to try to cover the diversity of different projects funded by the HMP at once.

Day 1 covered a bit of introduction and then a diversity of HMP related and some not so related (but good) talks.  The talks were perhaps a bit too reviewy for my liking, but I think actually, all of them were interesting.  Some lessons I got from today include the following:

1. The human microbiome is becoming a fascinating area of research with an ever growing set of data to look at
2. The data for the HMP seems to be openly available, which is good. Reference genomes can be found here. Some rRNA data can be found here. Strains of microbes are available too.  Not sure where the metagenome data.
3. Ease of access and use of data is more important than just access to data; the HMP DACC is doing a decent job with helping access data.
4. As important as access is metadata about samples. Not sure how much of this is available right now nor how easy the metadata is to make sense out of.
5. As with most (all?) large scale, top down projects, there are multiple areas where improvements could be made in communication and engagement with the broader community.  It seems like the HMP is working hard on this issue.
6. There are some possible complicated issues around release of microbiome data and medical records from people
7. There is still a big risk in overselling the potential benefits of microbiome research
8. Correlations ≠ causation.  Sorry I had to put that here.  See #7 above.
9. Analyzing and making sense of metagenomic data is still very very hard
10. We desperately need more ecology driven studies of the microbiome
11. To me, the HMP should really try to mimic the human genome project and focus on producing reference data (genomes, metagenomes, and rRNA) for everyone to use.  Trying to do complex scientific/clinical studies in this project seems inappropriate.  We all need the baseline to do the science.
12. As with every meeting, the best stuff that happens is in between talks.
13. Having the meeting room be something like 40 °C is probably not the best idea nor use of resources (hotel issue, not HMP issue).

Those are some of the lessons I am thinking about now, a few hours after the last talk.  But if you want to get a “real time” feel for the talks, the best way to do this, if you weren’t here, is to look at twitter posts about the meeting.  If you do not know, the common practice these days is to use a code within twitter specific for the meeting called a hashtag.  For this meeting the hashtag is #HMP2010 and you can find the tweets about the meeting easily by searching twitter for this code.  There were other twitter posts about the meeting, but may be somewhat hard to find b/c they did not use this code.  Such is life I suppose.

Anyway, if you want to see all the tweets from the first day of the meeting with this hash tag I have appended them at the bottom of this email.  This includes anyone who may have reposted (aka retweeted) these tweets to their twitter feed. 

Day 3 of trip, Day 2 of meeting.

Anyway, since I was up so late working on the blog post, I overslept and missed the first few talks,  I was really really bummed about this because one of the ones I missed was from Floyd Dewhirst who does some absolutely fascinating stuff.  I also missed a talk by Susan Haake.  Bummer.  But talks did start really early.

Fortunately, I got there in time for most of Jeff Gordon’s talk.  I simply am in awe of Jeff Gordon.  He is to me, the grand guru of the field of human microbiome research.  He has in particular specialized in making studies of germ free animals a key part of work on the microbiome.  I have always had very positive interactions with him, although I think he may still want to get back at me for including him in my April Fools joke about Craig Venter sequencing his own microbiome.

• Jeff Gordon discussed his current work on using germ free animals to study function and ecology of microbial communities
• RT @TheGenomeCenter Next talk Jeff Gordon from @wustl on the marriage of comparative metagenomics and gnotobiotics#HMP2010
• RT @TheGenomeCenter Gordon: took fecal microbe community from healthy donor and graft it into gut of germ-free mice successfully #HMP2010
• After brief delay now at #HMP2010 – Jeff Gordon up: creating artificial communities of many species & introducing to germ free animals
• Gordon: using defined communities of microbes to test microbiota response to different diets#HMP2010 – track changes in abundance, txn, etc
• Gordon : using RNAseq to track gene expression patterns in model microbial communities #HMP2010
• Gordon: Goal .. use “personal” culture collections isolated from people to get a collection that has coevolved w/ each other #HMP2010
• Gordon – much of OTU diversity in human gut microbes can be captured via culturing #HMP2010; though this ignores w/in species diversity
•  Jeff Gordon has electrified the crowd w/ his discussion of model organisms & model communities#HMP2010 #modelorganisms
• Liping Zhao discussed microbes associated with metabolic syndrome
• Now Liping Zhao from Shanghai Center of Systems Biomedicine on re-eng. gut microbiota with TCM foods to prevent metab. syndrome #HMP2010
• Zhao: multiple models could explain connection between microbes and obesity #HMP2010
• Zhao: who is right? Grandma: you are what you eat; Geneticists: you are your genes #HMP201
• Good to sea some old school TFLP Data here from Zhao mixed in with sequence data #HMP2010
• Zhao: what is connection between diet, microbiome and longevity? Doing experiment in mice over four years #HMP2010
• Zhao: diet / excercise differences -> lifespan differences + microbiota differences; though I note just correlations right now #HMP2010
• Zhao emphasizes benefits of having reference genomes to sort through metagenomic data #HMP2010
• Zhao wants to encourage marriage of metagenomics and metabolomics in gut studies #HMP2010

Then there was a brief break and then more talks.  Much of this has blurred together now so I think my tweets will be the best record of what happened from my point of view.

• Joe Petrosino discussed metagenomic projects at Baylor
• Now Joseph Petrosino from Baylor on improved metagenomic sequencing and analysis for healthy and diseased individuals #HMP2010
•  Joe Petrosino from Baylor giving overview of role of Baylor in HMP #HMP2010
• Petrosino – reminds people that not only is HMP producing data and science, but also spin off benefits akin to space program #HMP2010
•  Petrosino: key ?s: what are biases, how do new sequencing platforms perform, what is gained/lost from assemblies #HMP2010
• Petrosino has interesting results on sequencing mock community, I note we have study like this in PLoSonehttp://bit.ly/cPaIKF #HMP2010
• Petrosino doing some interesting analysis of the risks/benefits of assembly in metagenomics #HMP2010
• Note of caution: For statement “X manipulations of microbes help treat X ailments in X people X of the time”: X=”some” NOT “all” #HMP2010
• Petrosino working on a viral metagenomic sequencing pipeline including isolation, concentration strategies#HMP2010
• Phil Tarr discussed microbes associated with necrotizing enterocolitis
• Next up – Philip Tarr on the infant microbiome and necrotizing einterocolitis #HMP2010
• I have created a PaperLi newspaper on the human microbiome meeting tweets – seehttp://www.paper.li/tag/HMP2010 #HMP2010
• Phil Tarr telling a very sad story of a premature infant dying of necrotizing enterocolitis – which is alas very common #HMP2010
• Phil Tarr doing “massively parallel stool collection” for necrotizing enterocolitis study “all stools all the time” #HMP2010
• Tarr: high throughput, barcoded, quick collection of all stools of premies in hospital, then if some get NEC will do sequencing #HMP2010
• Tarr doing a great job of saying who did the analysis for which he presents results #HMP2010#willtrytodothisbetter
• Vincent Young
• Next up Vince Young on the role of gut microbiota in ulcerative colitis, IBD #HMP2010
• Young: many studies suggesting possible connection between microbes and IBD; but emphasizes these are associations not causal proof #HMP2010
• Young: complexities in IBD microbe studies incl. lack of time zero, diversity of host history/genetics, no info on microbe function #HMP2010
• Young looking at “pouchitis” to develop in IBD patients who get inflammation of diverting intestinal pouch#HMP2010
• Those interested in IBD/microbes might want to look at ileal transplant study from my lab/Georgetown http://bit.ly/XFRWf #HMP2010
• J. Dennis Fortenberry
• Dennis Fortenberry: urethral & coronal sulcus microbiome studies of adolescent males; offers caution for sexual nature of talk #HMP2010
•  Fortenberry “for those of you who have not been thinking about male sexual anatomy this morning, here is a primer” #HMP2010
• RT @TheGenomeCenter Fortenberry: multiple microbiomes of the penis – in areas where pass urine and areas used during sex#HMP2010
• Fortenberry discussed scanner image of MF sex, how microbes could exchange, ended w/ “don’t how how they got them in scanner” #HMP2010
• Fortenberry on difficulty studying microbe-sexual activity connection in teens “These are free-ranging adolescents” #HMP2010
• Fortenberry: need to train teens “amazing the things teenage males will do with specimen cups that does no involve peeing in cup” #HMP2010
• Fortenberry discussing ethical issues w/ genomic research on young people; especially on sexual behavior #HMP2010

Then lunch.  I sat again with some people from JCVI including Granger Sutton and Shibu Yooseph.  And I tried to get out of there quickly to get a bit of time to walk around, but it was hard to escape.

Then came the concurrent sessions which made me write this:

• Oh no – #HMP2010 has concurrent sessions – where to go? Where to go?

Here are some of my notes from the concurrent session talks I went to:

• Gail Rosen discussed metagenomic binning methods
• Listening to Gail Rosen talk about naive bayesian classifiers for metagenomic data #HMP2010
• @ianholmes yes i think kmer classification though got in late
• @phylogenomics “naive Bayesian classifiers for metagenomics” = clustering using k-mer composition of reads?
• Here is a link to Gail Rosens Naive Bayesian Classifier tool for metagenomics analysishttp://nbc.ece.drexel.edu/ #HMP2010
• Here is a link to Gail Rosens Naive Bayesian Classifier tool for metagenomics analysishttp://nbc.ece.drexel.edu/ #HMP2010
• Tom Schmidt discussed culturing microbes 
• Tom Schmidt now up talking about culturing the human microbiome #HMP2010
• Schmidt: Great Plate Count Anomaly misinterpreted to mean most microbes are unculturable – means most don’t grow in one condition #HMP2010
• Schmidt – cultured organisms very valuable for working on functions in communities #HMP2010
• Schmidt discussing nice trick for tracking oxygen in tissues – GFP only fluoresces win essence of oxygen#HMP2010
• Schmidt: to study microbes in colon they developed methods to do colonoscopies on unprepped people so microbes not flushed out #HMP2010
• Schmidt: in trying to culture from human microbiome have to switch methods and samples often to continue to recover new things #HMP2010
• Anthony Fodor discussed CF infections
• Anthony Fodor: how do infections in CF patients respond to antibiotics? Followed CF patients during exacerbation events #HMP2010
• Fodor pronounces T-RFLP “Tee R Flip” while I and I think others usually say “Tee Riff Lip” – I think I like his more #HMP2010
• Fodor – OTU diversity (i.e., number of bacterial species) is lower in severe CF infections #HMP2010 though he notes small sample size
• Diane E. Hoffmann discussed federal regulation of probiotics
• Listening to a Diane Hoffman discussing federal regulation of probiotics – there is lots of misleading stuff out there #HMP2010
• Hoffman: for most probiotics we know very little about effectiveness, safety, mechanisms and other key parameters #HMP2010
• Hoffman: whether/how to regulate probiotics depends on health claims, whether in food or not, etc.#HMP2010
• Many probiotics sellers make structure/function claims like “x promotes intestinal health” – these are less regulated #HMP2010
• Hoffman: FDA regulates health claims probiotics though FTC can also be involved if claims in media#HMP2010
• Hoffman: some think probiotics overregulated (making research harder); others think underregulated (bogus stuff out there) #HMP2010

The worst part of the concurrent sessions was that the schedules somehow got switched in some of them and I missed talks by both Rob Knight and Jeroen Raes.  Completely bummed about this as both are great.  Rob Knight apparently discussed his push for an Open Microbiome Project which I think is brilliant.

After the concurrent sessions I had coffee with a post doc candidate from Wash. U and then wandered back over to the hotel lobby to see if I could find someone who wanted to go to dinner.  I saw Peer Bork and Jeroen Raes having a beer and sat down with them with a plan to go to dinner in a bit. Dusko Ehrlich eventually sat down with us too as did a few others.  Eventually, Peer and Dusko headed off I think to work on their talks for the next day and Jeroen and I wandered off for dinner.  We bumped into Gail Rosen and one of her students and we all went to a pub, had dinner, and eventually I headed back to the hotel to do my bedtime stories activity with my kids again.

Then I wrote up a post on notes from Day 2 of the meeting, which is always good to do while things are fresh in ones head.  Here is what I wrote

Well, Day 2 is over now for the Human Microbiome Meeting.  See my previous post for information about the meeting and about Day 1. I enjoyed Day 2, though some things are starting to wear me down a little bit.  In particular, the fact that the meeting starts at 8 AM, or 6 AM California time, has been really rough.  I missed the first 1.5 talks today because of that.  Not to organizers of meetings everywhere – don’t start meetings so early.  And don’t have too many talks in one day.  It is better, far better, to just have fewer talks, than it is to wear people out.  Also not to meeting organizers – do not change the order of talks in concurrent sessions at the last minute.  Very bad idea.  Anyway – onwards.

As with Day 1, I think the best way to get a feel for the meeting would be to look at Twitter posts with the hashtag #HMP2010.  Unlike what I did with my post for Day 1 I am going to put only my tweets below, not everyones.

Today was split up into one series of talks in the AM and then concurrent sessions in the PM.  What lessons did I learn today?  Well here are a few, with some overlap to those on Day 1 but that is OK by me.

1. Again – correlations ≠ causation.  Those of you out there who do not get this should GTF out of science.
2. For statement “X manipulations of microbes help treat X ailments in X people X of the time”: X=”some” NOT “all”
3. Seems like we are really on the cusp of publications of 100s of clinical studies of microbes and their association with health status
4. Some of these studies are even starting to get at causation
5. It should be remembered that all of the methods used in microbiome studies are just methods; none are per se better than others; it is the science that should be judged not the tools themselves
6. With some effort it seems one can culture many more organisms from a system than might be expected
7. Cultures have many many uses
8. But culture based studies do not really get at population genetic frequencies and relative abundance information very well
9. Be wary of those who stick relentlessly with one idea or method
10. Very strange how few pharma reps there were here (more on this in my next post)
11. Please please please do not confuse data with knowledge.  Data can be very very useful and I completely support some projects that just are focused on generating data sets.  But knowledge comes from thinking about the data, and carefully analyzing it.
12. Microbes, I think, run our lives much more than we would like to believe

Anyway – that is a brief update.  Back to preparing my talk for later this AM …

Finally, I got to work on my talk.  Wow that took a while.  I was up until about 3 am.  Finally I got to sleep a bit worried about missing my alarm ..

Day 4: My talk and heading home

Got up with plenty of time to spare, worked a bit on my talk, got my stuff together, grabbed a coffee, and went to set up my presentation. Peer Bork was already there getting his set up. The AV guy was not pleased that we all wanted to present off of our laptops. He said “We have a mac you can use”. I asked if they had keynote and they did not. Not very useful. Got myself set up and then paced around waiting for the lovely 8 am start. And then we were on.  Here are my tweets from just before my talk:

• Attn Apple Keynote experts: anyone know how to hide the flashing volume bar when using “record slideshow” option?
•  In relation to my upcoming talk at #HMP2010 I thought I would share this 2007 April Fools story about microbiomes http://ff.im/-q6t01
• Next up at #HMP2010 Jonathan Eisen, aka, me: the Genomic Encyclopedia of Bacteria & Archaea & the dark matter of the genomic universe

I note, I tried to record my talk but that did not work for some reason.  I did post my slides on slideshare here.  And I think I can embed them in this post

Here are my notes on the rest of the talks in that AM session.

• Peer Bork: Towards Microbial Markers for the Human Gut Microbiome
• Now Peer Bork from EMBL on microbial markers for the human gut #microbiome #HMP2010
• Peer Bork now discussing covariation of gene families within Metagenomic data sets #HMP2010
• Bork: analyzing metahit data on metagenomics of the human gut #HMP2010
• Bork: developed a metagenomics pipeline called SMASH which should be available soon #HMP2010
• Bork: does some interesting comparisons of phylogenetic vs. Functional composition in Metagenomic samples; #HMP2010
• Bork: tries to remove vagrants (e.g., organisms in food) from Metagenomic data sets by looking at habitat of reference genomes #HMP2010
•  Bork: w/ small sample get three distinct clusters of co-ocurring gene families within human Metagenomic samples #HMP2010
• Bork: then went to analyzing newer Metagenomic Illumina data w/ more samples – get three major clusters of coocurring genes again #HMP2010
• Bork – also sees three distinct clusters of coocurring rRNA types in human samples #HMP2010 – he now calls these enterotypes
• Bork – can find specific functional categories that correspond to the three distinct Metagenomic types#HMP2010
• Bork – can find specific functional categories that correspond to the three distinct Metagenomic types#HMP2010
• Bork: shows cool pathway analysis iterated along fine scale transecting in hypersaline samples, showing as pathways shift #HMP2010
• Bork : we need better databases of pathway-gene mapping in diverse organisms and diverse phenotypes#HMP2010
• Dusko Ehrlich discussed the metahit project 
• Next: one of most entertaining people in field: S. Dusko Ehrlich discussing the MetaHit approach to relation between microbes & us #HMP2010
• Ehrlich: discussing the BGI/MetaHit Nature metagenomics paper which I personally found fascinating#HMP2010
• Ehrlich: in gut metagenomes, a high fraction of all genes are shared between people; same true for species#HMP2010
• Ehrlich: much of the variation between people in metagenome is in relative abundance not in presence/absence of genes or species #HMP2010
• Ehrlich: comparing metagenome of 177 Danish people; 67 lean, 110 obese, deep Illumina sequencing#HMP2010
•  Ehrlich: Identifying some microbial genes associated with host body mass index #HMP2010
• Ehrlich: the major differences between metagenome in obese vs. lean people are genes from Firmicutes#HMP2010
• Ehrlich shown a cool graph that he calls the Metahit barcode – 4 species x genes in rows, samples in columns ordered by BMI #HMP2010
• Here is link to the MetaHit human metagenome paperhttp://www.nature.com/nature/journal/v464/n7285/full/nature08821.html #HMP2010
• Ehrlich also doing metagenome analysis of IBD, says there are correlations but cautions we do not know causal vs. consequence #HMP2010
• Ehrlich now showing that his metahit barcode can potentially be used for strain level differences #HMP2010
• Ehrlich: we are on brink of having diagnostic tests, possibly better treatments, possibly novel treatments for health states #HMP2010
• Ehrlich ends by saying you should follow @metahit #HMP2010
• Excellent suggestion from crowd after Ehrlichs talk: we should look at microbiome in non industrialized populations #HMP2010
• Kanitsak Boonanantanasarn discussed oral cancers
• Boonanantanasarn looking at microbes associated with oral cancers #HMP2010
• Boonanantanasarn: see increase in archaea in samples from oral cancer vs. normal #HMP2010 #archaearule
• Heidi Kong discussed atopic dermatitis
• Now up Heidi Kong on the skin microbiome, atopic dermatitis and immunodeficiency #HMP2010
• Kong: how to move from correlation to causation?; using longitudinal studies, selective alteration of microbes, mouse models #HMP2010
• Yuzhen Ye discussed metagenomic informatics
• Awesome: Yuzhen Ye just used a drawing by her four year old w/ cryptic writing to discuss difficulty in Metagenomic analysis #HMP2010
• Ye now discussing her FragGeneScan Metagenomic gene finderhttp://omics.informatics.indiana.edu/FragGeneScan/ #HMP2010
•  Ye: working on assembling genes from within metagenomics data (and thus not doing assemblies of everything) #HMP2010
• Ye: has a metagenomic binner called abundancebin which not surprisingly using abundance information to bin #HMP2010
• Uploaded my slides for my #HMP2010 talk tohttp://slidesha.re/cQQkws
• Ye: describing SWIFT a fast protein similarity search method using reduced alphabet suffix arrays #HMP2010
• Daniel Haft, who I used to work with a little bit when we were both at TIGR then discussed protein family analysis
• Next up Dan Haft on tuning protein families from reference genomes to improve pathway analysis#HMP2010
• Dan Haft: discussing “equivalogs” – if you want to know meaning readhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC29844/#HMP2010
• Haft: 1500 genomes we have are intelligence intercepts from the microbial world .. If we can decode them, we can learn tons #HMP2010
• Haft rattling off series of enzyme names, types & actions, I wonder if others are as lost as I am; #HMP2010#biochemistryisnotforme
• Cindy M. Liu
• Next and last: Cindy Liu talking about the sinus microbiota in health and disease #HMP2010
• Liu discussing chronic rhinosinusitis – effects millions and costs lots (though kills very few) “We should help them” she says #HMP2010
• Liu discussing need for ecological models of stable states in human microbiome studies #HMP2010
• And #HMP2010 is done; overall I enjoyed it; will post thoughts on day 3 later

And then, just like that, the meeting was a wrap. I checked out, chatted a bit with a few people, and then off to the airport and home.  If you have gotten this far in this post, I am impressed …  I am going to hold off a few days before writing up a summary of what I learned from the meeting overall but I think the lessons learned from Day 1 and Day 2 are a good place to start.  Thanks for reading.

———————–
Also here are some other links of relevance to the meeting

• http://futureofgenomicsblog.org/HMP/ 
• http://twapperkeeper.com/hashtag/HMP2010
• Posts from Mike the Mad Biologist
• Too Many Grand Old Man Talks
• What’s Going on with the Explosion of Hotel Bed Pillows?
• A Benefit of the Human Microbiome Project: Putting the “99% of Bacteria Are Unculturable” Canard to Rest
• Human Microbiomics Live News – HMP_2010
• Ruchira Datta’s notes on FriendFeed