2017 Innovation Lab on Quantitative Approaches to Biomedical Data Science Challenges in our Understanding of the Microbiome

Quick post here sharing an interesting sounding event “2017 Innovation Lab on Quantitative Approaches to Biomedical Data Science Challenges in our Understanding of the Microbiome“.   From the website:

 

The BD2K Training Coordinating Center is organizing an Innovation Lab to foster new interdisciplinary collaborations among quantitative and biomedical researchers to address data science challenges in our understanding of the microbiome. The scope of microbiome, as defined here, broadly describes the corresponding high-dimensional big data derived from microbiota associated with a health or biomedical research objective. A more detailed description of the Lab can be found in the document Detailed information on 2017 Innovation Lab. Some exemplar areas of quantitative interest are suggested in the document Quantitative Topics of Expertise Needed and biomedical interest are suggested in the document Biomedical Topics of Expertise Needed.

The Innovation Lab process entails participation in an intensive five-day residential workshop in order to facilitate the development of new teams of early-career biomedical and quantitative investigators who generate multidisciplinary cooperative research programs through a real-time and iterative mentoring process. The concept of the Innovation Lab program is to organize intensive multidisciplinary interactions involving around 30 participants, with the aim of developing new and bold approaches to address grand challenge questions for topics that could benefit from a fresh or divergent perspective. Prior knowledge of research at this interface is not required; rather, applicants with either quantitative or biomedical expertise who demonstrate their willingness to engage in collaborative multidisciplinary research are sought. Teams are highly encouraged to develop proposals for submission to the funding agencies after the conclusion of the workshop. Professional facilitators and senior scientists (mentors) with relevant expertise and exposure to the topic area assist the participants. The scientific experts serve as mentors and act as impartial referees during the process. Working under the guidance of the mentors, participants will form teams during the workshop to develop interdisciplinary projects to solve a data science challenge arising from a biomedical research question involving the microbiome.

The lab will include opportunities for learning about NIH and NSF funding through interaction with program officers.

Application Procedure:

Applications accepted Starting February 1, 2017
DEADLINE TO SUBMIT APPLICATIONS:
11:59PM, Eastern Time, Sunday, March 12, 2017
 

Applications will be considered from researchers in quantitative disciplines (mathematics, statistics, computer science, engineering, as well as other data-intensive areas including but not limited to finance, physics, climate modeling, and astronomy) and biomedical disciplines (including but not limited to biological, behavioral, social, environmental, and clinical domains). Researchers coming from a broad diversity of quantitative and biomedical backgrounds are encouraged to apply. Researchers in the biomedical domain must demonstrate their experience working with microbiome big data (e.g. data from sources including but not limited to whole or metagenomics analyses, transcriptomics, metabolomics, or other big data approaches involving microbial communities from human and/or other environmental niches with a health or biomedical research implication). A committee will select approximately 30 applicants to take part in the Lab. Selected participants will have their travel and hotel expenses fully covered by BD2K TCC. Applicants must be willing to commit to stay for the entire Innovation Lab.

GSC19 (Brisbane, Australia) Registration is Open !!

We are happy to announce that registration for GSC19 is now open !!

Theme:  Extending Standards to Viruses and Microbial Eukaryotes
Date: May 15th-17th, 2017
Location: Stamford Plaza, Brisbane, Australia
Host: Philip Hugenholtz          
Australian Centre for Ecogenomics, University of Queensland
The agenda is packed with exciting sessions and topics:
  • Viral classification and genome standards
  • Microbial eukaryote classification and genome standards
  • Bioinformatic workflow standards (large scale, reproducible, cost-effective)
  • Microbiomes of Australia
  • Modes and tempo of evolution
  • Genome taxonomy
Check out specific session details and confirmed speakers on the GSC19 homepage.  Please direct GSC19 inquiries to the GSC contact page.
Meeting Organizers:Philip Hugenholtz, Caroline Moniz, Lynn Schriml, Folker Meyer and Pelin Yilmaz
We are looking forward to seeing you in Brisbane !!
                        

Quick post: Drosophila Genotype Influences Commensal Bacterial Levels in Lab Reared Flies

Just a quick post here.  This is an interesting paper on how genotype of Drosophila influences their microbiome. As a side story – I think flies could become an interesting and useful model for studying how the built environment (e.g., vials, cages, food, etc) influence microbiomes.

Host genotype can influence the composition of the commensal bacterial community in some organisms. Composition, however, is only one parameter describing a microbial community. Here, we test whether a second parameter—abundance of bacteria—is a heritable trait by quantifying the presence of four commensal bacterial strains within 36 gnotobiotic inbred lines of Drosophila melanogaster. We find that D. melanogaster genotype exerts a significant effect on microbial levels within the fly. When introduced as monocultures into axenic flies, three of the four bacterial strains were reliably detected within the fly. The amounts of these different strains are strongly correlated, suggesting that the host regulates commensal bacteria through general, not bacteria-specific, means. While the correlation does not appear to be driven by simple variation in overall gut dimensions, a genetic association study suggests that variation in commensal bacterial load may largely be attributed to physical aspects of host cell growth and development.

Source: Drosophila Genotype Influences Commensal Bacterial Levels

The concept of hygiene and the human microbiome.

(This post was written by Roo Vandegrift at the University of Oregon)

I was recently asked to spearhead the writing of a review centered around the interaction between the concept of hygiene and our increasingly nuanced understanding of the human skin microbiome for the Biology and the Built Environment (BioBE) Center at the University of Oregon.

This review began with an invitation from Dyson to conduct an impartial review of hand drying studies, which have been mired in competing interests and faulty methods. We saw an opportunity to not only provide an unbiased review of the literature, but also to ask a more fundamental question: how should hygiene be defined in light of our evolving perspective of the human and indoor microbiome?  We delivered a brief summary to Dyson (here) and then built upon that work to develop this question.  

As we started digging into the body of literature on hand hygiene, two things struck us as peculiar: the first was that in the hundreds of studies explicitly examining hygiene, the concept was never explicitly defined; the second was that there seemed to be a clear division between skin microbiological investigations coming from clinically and ecologically informed perspectives, with clinical research generally relying on older cultivation-dependent techniques. These two issues became the drivers for our review, and our goal was to provide an explicit definition of hygiene that would help to bridge the gap between the clinical skin microbiology literature and the newer human-associated microbial ecology literature. We were then able to use the body of literature on hand drying as a case-study to examine the implications of using a microbial ecology-based approach to defining hygiene.

You can read the full review as a preprint on bioRxiv now: http://biorxiv.org/content/early/2016/12/20/0957450

You can read the shorter, white page summary of the review on the BioBE blog: https://biobe.uoregon.edu/2016/11/04/cleanliness-in-context

Our review is broadly split into three sections: one section summarizing previous work on hygiene, one section briefly outlining previous work on human-associated microbial communities (including those found on the skin and in the built environment), and one section attempting to synthesize the two.

In the first section, we start seeing some of the limitations of cultivation-dependent methods, and how those limitations combine with implicit assumptions about the concept of hygiene. One thing that stands out to me from a thorough reading of clinical literature on hand hygiene is how often the idea of sterilization is used as a stand-in for the idea of hygiene — one result of the complete adoption of the germ theory of disease is the common misconception that “all microbes are germs”. This is apparent in the majority of studies of hygiene, particularly reflected in the focus on bulk reduction in microbial load, regardless of the identities of those microbes. I would, however, like to acknowledge Allison Aiello and Elaine Larson’s careful 2002 review, “What is the evidence for a causal link between hygiene and infections?“, which goes considerably beyond thinking of all microbes as germs and examines hundreds of studies, pulling out those that actually examine health outcomes as a dependent variable. Their review lays the conceptual foundations for what we are trying to do in our review.

In bridging into the second section, which outlines human-associated microbial ecology, we wanted to clearly illustrate the advances in techniques that the field utilizes. We put together this simple, but hopefully informative, conceptual figure to help:

Figure 1: Cultivation-dependent methods (A) are commonly used to study aspects of hand hygiene; many microbes are not detectable using this methodology (represented in grey). Handwashing reduces bulk microbial load, and cultivation yields data showing changes in the numbers of colony-forming units (counts); some studies identify colonies using morphological or molecular methods, yielding limited taxonomic information. Cultivation-independent methods (B), including high-throughput DNA sequencing, are commonly used to study the microbial ecology of the skin. Using these methods, it is possible to quantify alterations in relative abundance of bacterial populations with treatment (such as handwashing), obtain deep, comprehensive taxonomic diversity estimates; depending on technique, it may be possible to also obtain information on functional metabolic pathways (using metagenomics), assessment of proportion of the community that is active (using rRNA / rDNA comparisons, or live/dead cell assays), among other things.

It is clear that hygienic practices may interact significantly with human-associated microbial ecology. We highlight and summarize some of the important ecological factors that may interact with hygienic practice in a second conceptual figure:

Figure 2: Conceptual illustration of important ecological factors impacted by hygienic practice. Dispersal (a) is the movement of organisms across space; a patch of habitat is continuously sampling the pool of available colonists, which vary across a variety of traits (dispersal efficiency, rate of establishment, ex host survivability, etc.) (Vellend 2010); high dispersal rates due to human behaviors (e.g., microbial resuspension due to drying hands with an air dryer) have the potential to disperse both beneficial and harmful bacteria alike. Protective mutualisms (b) function through the occupation of niche space; harmful microorganisms are excluded from colonization via saturation of available habitat by benign, non-harmful microbes (Poisot et al. 2014). Host/microbe feedbacks (c) occur via the microbiota’s ability to activate host immune response, and the host immune system’s ability to modulate the skin microbiota (Chehoud et al, 2013; Garcia-Garcera et al, 2012; Oh et al, 2013) — multiple pathways, including IL-1 signalling (Naik et al 2012) and differential T-cell activation (Seneschal et al 2012), are involved — such feedbacks between host immune response and the skin microbiota are thought to be important to the maintenance of a healthy microbiota and the exclusion of invasive pathogenic microbes (Zhang et al 2015). Environmental filtering (d) works on the traits of dispersed colonists — microbes that can survive in a given set of environmental conditions are filtered from the pool of potential colonists (Vellend 2010): the resources and conditions found there permit the survival/growth of some organisms but not others. The importance of diversity of the microbiota to each of these ecological factors should not be underestimated; interactions between taxa may modulate their ecological roles, and community variation across a range of ecological traits may be altered by changes in community membership or structure (HMPC, 2012).

Coming to the third and final section, it should be clear to the reader that future work on hygiene would benefit from integrating modern techniques and an ecological perspective from recent human microbiome research. To facilitate that, we believe that it would be helpful to have a clear, concise definition of hygiene from which to work. This is probably the most important moment from our paper:

The evidence that microbes are essential for maintaining a healthy skin microbiota supports the idea that hygienic practices aimed at the simple removal of microbes may not be the best approach. Rather, hygienic practices should aim to reduce pathogenic microorganisms and simultaneously increase and maintain the presence of beneficial microorganisms essential for host protection. It is clear that microbial colonization of the skin is not deleterious, per se. Humans are covered in an imperceptible skim of microbial life at all times, with which we interact constantly. We posit that the conception of hygiene as a unilateral reduction or removal of microbial load has outlived its usefulness and that a definition of hygiene that is quantitative, uses modern molecular biology tools, and is focused on disease reduction is needed. As such, we explicitly define hygiene as ‘those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease’.

Let me repeat that last part: we explicitly define hygiene as ‘those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease’. We feel that it is incredibly important to define hygiene in terms of health outcomes, not just in terms of reduction in number of microbes. This allows for research (consider, for example, probiotics research) to address the root of hygienic practice: cleanliness in pursuit of improved health.

From the hand drying example, it is clear that a standard definition of hygiene would be helpful: it turns out the vast majority of research on the hygienic aspects of hand drying has been funded by either the paper towel industry or the blow drier industry as advertising tools. There appears to be something of a feud going on between these two competing industries. Sadly, there is much about the current state of hand drying literature that is clearly partisan, and it is difficult to evaluate claims from either side because they define hygiene differently.

The hand drying literature can be separated into two opposing divisions: one attempting to demonstrate that the newer air dryers are as hygienically efficacious as paper towels, and the other attempting to discredit the newer technology in favor of paper towels. While both divisions utilize bulk reduction in microbial load as a proxy for hand hygiene, research from the first division largely focuses on the potential of wet hands to transfer microbes and the ability of air dryers (whether warm or jet) to effectively dry hands: the hypothesis in this case is drying is hygienically efficacious if hands are dry and new microbes are not acquired through the process. Research from the second division tends to focus on the risk of air dryers to spread microbes throughout the environment by aerosolizing moisture from the hands: the hypothesis in this case is drying is hygienically efficacious if new microbes are not acquired through the process and if production of aerosols are minimized. It is difficult to compare the two divisions because many of these studies include methodological issues (e.g., variation in protocols, lack of appropriate controls or statistical analyses) that make it difficult to compare results across studies.

Despite there being an obvious interplay between these two divisions, many of the concerns on either side remain unaddressed. Utilizing a definition of hygiene that explicitly relies on reduction in disease spread would address concerns on both sides of the debate: there is currently no evidence linking aerosolization of residual moisture (and associated microbes) with the actual spread of disease. Likewise, despite demonstrations that wet hands allow for increased bacterial transmission, there does not seem to be evidence linking wet hands after washing to deleterious health outcomes. The complex ecological context of the hand microbiota may modulate effects of both aerosolization and prolonged moistening. Additionally, the majority of hand drying research largely ignores the relative hygienic contribution of the hand washing step; understanding the relative contribution of washing to hygienic efficacy is necessary to put the hand drying literature in proper context.

The experience of working on this review has been incredibly positive: I’ve gotten to read deeply in corners of the scientific literature that I would not have expected I would be delving into even six months ago, I’ve learned a number of beautiful and startling things, and I believe that we have been able to contribute something necessary and worthwhile to the scientific discussion of hygiene. There is a gradual paradigm shift occurring right now in the clinical sciences, with germ theory being gently replaced by a more nuanced theory of disease that takes into account the beneficial role that our symbiotic microbiome plays; this review, I hope, will be a helpful building block for that new paradigm.

The “Koala Poop Microbiome” Class at UC Davis

You know sometimes you use a working title for something for long enough that it becomes the title? Like “Snakes on a Plane”.  That’s what happened in this case,  we also meant to come up with a name for this class… never did and so the official name at the registrar is “Koala Poop”.  Awesome.

So last Spring quarter Ashley Vater and I teamed up to teach a “Swabs to Genomes” class here at UC Davis.  Our summary of the class, with course materials, can be found here at microBEnet.   The big problems with that class were the cost and difficulty of genome sequencing in only 10 weeks.  So this time, Ashley, Katie Dahlhausen and I decided to try a version that focused more on the microbiology, without genome sequencing.  We also took ideas from a similar class taught by Cameron Thrash at LSU.

The background for this project is Katie’s PhD work which focuses on the koala gut microbiome.  Her crowdfunded research project is looking how koalas (which require bacteria to break down tannins in their limited diet) respond to antibiotic treatment (for rampant Chlamydia infections).  In this class, the students are attempting to isolate ~100 bacterial strains from koala feces under several combinations of conditions; anaerobic/aerobic, RT/37C, tannin positive/negative, BHI versus LB versus CBA media.  They will isolate the bugs, extract DNA, perform 16S Sanger PCR, identify the bugs (including making phylogenetic trees), and then screen these isolates for resistance to 10 common antibiotics (including the two actually used with koalas).

As with the last class, we are requiring the students to blog here on microBEnet as part of the class, although this time we’re adding a “peer review” component to the process which will delay the posts a bit.   Those blogs will be found on a dedicated page here, and at the end of the quarter I’ll post a summary of the class, along with the results and all the class materials.

Stay tuned!

Koala Poop Microbiome Class: Week 2, Picking Colonies

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10 colonies selected for dilution streaking

(This blog post was prepared by students enrolled in the Koala Poop Microbiome Class in the Fall of 2016 at UC Davis)

The goal of this week was to isolate a single bacterial colony for further study. This week  we observed bacterial growth from our koala poop samples. With a partner, we obtained and observed the individual plate cultures from Week 1 to see if anything had grown. We then chose and labeled 10 colonies, particularly ones that were large in size and clearly isolated from other colonies. In order to start the process of dilution streaking, we first obtained 10 new agar plates. Each pair made sure that these new agar plates had the same media type as Week 1.

We hope to identify the kinds of plates that the isolates were most prevalent on, and maybe how media relates to the koala’s diet. With this isolated bacteria, we will be able to carry on with the experiment and extract DNA (Week 3!). Click here to learn more information about dilution streaking.

It was interesting to find several different kinds of bacteria in the petri dishes prepared last week. Looking around the lab, we could see tannin-degrading bacterial colonies that were on many of the plates ! The dilution streaking was a little challenging since we had to switch inoculating loops  to do it properly, and the agar could be easily punctured up with the loops. Keeping track of the plates used was confusing because some of us not only used our own plates, but also used plates from the Australian collection in order to get the ten colonies required per group.

In preparation for Week 3, the class also practiced using micropipettes. In table groups, we learned to efficiently pipette small amounts of water in and out of an eppendorf tube as part of a game. This was somewhat challenging because not everyone at our table had the same micropipette so each dial was labelled differently, however, it was a fun experience! Some questions coming into Week 3 are: What kind of bacteria colonies were on the plates? What bacteria was the most common among all the plates? Are there other methods similar to streak plating that isolate microorganisms?

 

 

Notes from talk by Andrew Moeller on “Evolution of the human gut microbiome”

Andrew Moeller gave a talk at UC Davis Tuesday on “The evolution of the human gut microbiome”.  He is a post doc at UC Berkeley working in the Nachman lab.  I did not have a working computer so – gasp – I took notes with paper and pen.  The talk was quite interesting and I thought some people might find some parts of interest.  So I am posting the notes here.  I note – I talked to him a bit about adding more of a “Built Environment” component to some of his work and I hope he does.  That is kind of a new mission of mine and microBEnet’s – to reach out to microbiome and microbial ecology researchers and see if there is a useful way for them to add a BE component to their work.

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The ultimate embodiment of modern day germophobia: Squix 

Well, I am truly speechless about this.  Katie Dahlhausen, a graduate student in my lab, pointed me to this last week

SQUIX | Innovative Germ Fighting Products

and I have been wondering what I could possibly say about it.  So I think I am just going to not write anything else but I will post some clips from the SQUIX site.  There are just a sampling.  Please check it out.  And please, do not order anything from this place.  Yes, keeping clean can be a good thing in the right circumstances.  But overdoing it by surrounding yourself and your kids and your pets and your office and your home with antimicrobial everything AND wiping and washing and spraying and irradiating everything around you almost certainly is not a good thing unless you run an surgery clinic for people with compromised immune systems.
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Dragons and their Microbiomes – really

OK so I love Komodo dragons.  I love microbes and microbiomes.  And I am an editor at mSystems.  So yes I am biased in all sorts of ways about this paper.  So with that caveat – I think this is definitely worth a look: The Oral and Skin Microbiomes of Captive Komodo Dragons Are Significantly Shared with Their Habitat by Embriette R. Hyde, Jose A. Navas-Molina, Se Jin Song, Jordan G. Kueneman, Gail Ackermann, Cesar Cardona, Gregory Humphrey, Don Boyer, Tom Weaver, Joseph R. Mendelson III, Valerie J. McKenzie, Jack A. Gilbert, Rob Knight
mSystems Aug 2016, 1 (4) e00046-16; DOI: 10.1128/mSystems.00046-16.

 

Abstract:

Examining the way in which animals, including those in captivity, interact with their environment is extremely important for studying ecological processes and developing sophisticated animal husbandry. Here we use the Komodo dragon ( Varanus komodoensis ) to quantify the degree of sharing of salivary, skin, and fecal microbiota with their environment in captivity. Both species richness and microbial community composition of most surfaces in the Komodo dragon’s environment are similar to the Komodo dragon’s salivary and skin microbiota but less similar to the stool-associated microbiota. We additionally compared host-environment microbiome sharing between captive Komodo dragons and their enclosures, humans and pets and their homes, and wild amphibians and their environments. We observed similar host-environment microbiome sharing patterns among humans and their pets and Komodo dragons, with high levels of human/pet- and Komodo dragon-associated microbes on home and enclosure surfaces. In contrast, only small amounts of amphibian-associated microbes were detected in the animals’ environments. We suggest that the degree of sharing between the Komodo dragon microbiota and its enclosure surfaces has important implications for animal health. These animals evolved in the context of constant exposure to a complex environmental microbiota, which likely shaped their physiological development; in captivity, these animals will not receive significant exposure to microbes not already in their enclosure, with unknown consequences for their health. IMPORTANCE Animals, including humans, have evolved in the context of exposure to a variety of microbial organisms present in the environment. Only recently have humans, and some animals, begun to spend a significant amount of time in enclosed artificial environments, rather than in the more natural spaces in which most of evolution took place. The consequences of this radical change in lifestyle likely extend to the microbes residing in and on our bodies and may have important implications for health and disease. A full characterization of host-microbe sharing in both closed and open environments will provide crucial information that may enable the improvement of health in humans and in captive animals, both of which experience a greater incidence of disease (including chronic illness) than counterparts living under more ecologically natural conditions.

Today & tomorrow – live webcast – Standards for Microbiome Measurements @NIST

Definitely worth checking this out. NIST is running a meeting on Standards for Microbiome Measurements

From the site:

This workshop will seek input on defining reference materials, reference data and reference methods for human microbiome community measurements. This workshop is sponsored by NIST and NIH’s National Institute of Allergy and Infectious Diseases and the Human Microbiome Project.

Over the past 10 years, advances in ‘omic technologies have resulted in a meteoric rise in our ability to understand the constituents and functions of complex microbial communities (microbiomes); and the profound effect that these microbiomes have on their hosts and the environment. However, the interlab comparability of measurements on microbiomes is generally poor. Biases exist along every step of the measurement process, from sample collection, extraction techniques, measurement technology employed (next-generation sequencing, mass spectrometry, nuclear magnetic resonance), and, finally, to data analysis and interpretation. There is a need for the adoption of reference materials, reference data, and reference protocols in order to identify and eliminate measurement bias.

Link for live Webcast: http://www.nist.gov/mml/standards-for-microbiome-measurements-webcast.cfm