megabiome – Jonathan Eisen's Lab

CRISPR Wars: The Microbes Strike Back

On January 14, Eric S. Lander published an article, The Heroes of CRISPR, in the journal Cell. This article was then thrust into the spotlight by enraged twitter enthusiasts who thought that the article downplayed the roles of both the University of California’s Jennifer Doudna and Emmanuelle Charpentier of the Helmholtz Center for Infection Research in Germany. However, all of the subsequent articles detailing the controversy surrounding the paper have failed to contact and interview a set of key players involved in CRISPR-Cas9. This key set of players, collectively known as “The Microbes”, has reached out to me via quorum sensing to explain their side of the story and their reaction to the article.

“We were a bit shocked and enraged after reading the article at how little credit that we, the Microbes, were given. Dr. Lander describes a ’20-year journey’ in his article, but we’ve been developing the CRISPR-Cas9 system for much longer than that, millions of years longer!”

Millions of years! Given the current climate of research, how difficult it is to get funding and the lack of first author papers they have published, I can definitely understand their anger.

“We developed the CRSIPR-Cas9 mechanism as a dynamic security system to keep out our pesky competitors, the Viruses. We never imagined that it would one day be used for gene editing, if we had we’d have utilized it on humans a long time ago to make them our slaves.”

I laughed. They didn’t.

What the world may have looked like when the Microbes started working on CRISPR.

What the world looks like now according to Dr. Lander’s paper. Whether or not the Microbes had anything to do with the disappearance of Greenland, Iceland and Latin America is currently under investigation.

Desiring a change of topic, I inquired as to how close the Microbes were to the researchers involved in engineering CRISPR-Cas9 for use as a genome editing tool.

“One might say that we are intimately close to the researchers involved. We are familiar with every aspect of their research, we know where they live, what they eat and what they did last summer…”

Cue to me looking around for the closest door through which I can escape. Since they sounded like they were, uh, such good friends, I asked how the Microbes felt about the allegations that the roles of Jennifer Doudna and Emmanuelle Charpentier were downplayed.

“We understand how they must be feeling and lament that their roles were downplayed. Many of our members are from underrepresented minority groups, and we are familiar with being overlooked or unable to thrive in various media and culture situations. Just like us, they should have been included in the paper which we propose be re-titled to ‘The Heroes, Heroines and Microorganisms of CRISPR’. “

At this point, it was quite clear that the Microbes were taking this situation very seriously. When I asked what they were planning on doing about the situation, they asked me to leave the room so they could consult a lawyer. When I returned they said:

“We have collectively decided to go on strike and to withhold our CRISPR capabilities until an agreement about our contribution and inclusion in the paper and also the CRISPR patent can be reached. Moving forward, we are also requiring that future research papers that use CRISPR include us an author; we will no longer tolerate research parasites.”

As the interview was ending, I asked if there was anything else about the article that bothered them. Their response took me by surprise.

“We took offense to the use of the word “strange” when describing our DNA sequences. You don’t see us calling your introns and exons “weird” or labeling your DNA as “junk” do you?”

No, I suppose not. Tonight, I’ll be raising a glass of wine to the real heroes and heroines of CRISPR, the Microbes.

Extraterrestrials, or Space Pirates?

A landmark study has illuminated the presence of specific microbes on the ISS strongly suggesting that humans might be on board the spacecraft. In a routine survey of one air filter and more than one (two) of the vacuum bags used to clean the station, the researchers arrived at unexpected results – the amount and type of microbes found on the ISS are in stark contrast to those found on the meticulously scrubbed and disinfected NASA clean rooms* back on Earth. Furthermore, these microbes on the ISS seem to resemble those found in association with humans.

NASA Clean room, image from Wikimedia Commons https://commons.wikimedia.org/wiki/File:327160main_SICDH_FS_img1_lg.jpg

Experts say that if these microbes came from a human, it is entirely possible that they could live on another human. A major worry is that the astronauts and cosmonauts expected to continue living and working now on the ISS might be living with bacteria, which have been known to cause disease in the past. It is therefore now the topmost priority to figure out which pathogens are there and how on (from?) Earth they arrived.

Astronaut_Karen_Nyberg_With_Cosmonaut_Fyodor_Yurchikhin_and_Astronaut_Luca_Parmitano-from-Wikidmedia-Commons-300x199.jpg

Astronaut Karen Nyberg with fellow Cosmonaut Fyodor Yurchikhin and Astronaut Luca Parmitano, image from Wikimedia Commons https://commons.wikimedia.org/wiki/File:Astronaut_Karen_Nyberg_With_Cosmonaut_Fyodor_Yurchikhin_and_Astronaut_Luca_Parmitano.jpg

Microbial forensic experts are being called in to analyze the unique “fingerprint” signatures of the microbes left behind, in the hope of identifying the suspects these potential pathogens came from. Preliminary findings have urged officials to focus their search on anyone who has recently eaten space-grown lettuce. Next steps to understanding what is influencing the microbes on the ISS include analyzing the effect of a human breathing, eating, washing hair, sneezing, farting, playing the guitar or performing any other act as might be expected of these hypothesized ISS inhabitants. Due to the limited knowledge of the on-goings of the station, the public is being asked for any information they might know of regarding such activities.

*Designed to eliminate the spread and survival of microorganisms.

Volkswagen: Diesel Transplants Reveal Likely Culprit Behind Deiselgate: Car Microbiomes

Screen-Shot-2015-10-06-at-9.30.41-AM-1038x576.png

By Morten Blaser

WOLFSBURG (AP) – Volkswagen held a press conference earlier today to present the results of their preliminary investigation into the “dieselgate” controversy.

Volkswagen’s CEO to be Hans Dieter Poetsch himself oversaw the press conference in Wolsfburg where the company presented the results of this investigation .

“We are determined to get to the core of the problems with the vehicle testing anomalies. We have begun testing many theories, including what we thought was the most likely explanation – that a rogue engineer in secret without the knowledge of anyone else wrote millions of lines of code to rig the smog tests” reported Poetsch. “Although this still seems plausible we have found another possible explanation, which has led us to hold this press conference today.”

Poetsch then turned over the lectern to Volkwagen’s Chief Scientist Josephine Candelsman. She gave a six hour PowerPoint presentation on the investigation. The key came right at the end:

“To test one possible explanation – we carried out a diesel transplant where we took the diesel from one vehicle that had failed the test and removed it and transferred it to another vehicle that had passed the test.”

The crowd was hushed when she reported the key finding:

“Amazingly, the recipient vehicle went from being lean, green and energy efficient to being an incredibly inefficient, pollution pumping vehicle. In other words, something in the diesel transferred the inefficiency from one vehicle to another.”

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Gordon then turned over the presentation to Volkswagen’s Chief Microbiologist Jeferina Gordon:

We ran the diesel from the donor and recipient vehicles through a series of tests – especially an array of genomic analyses. And what we found was that the microbes in the donor diesel were very different from those in the recipient. This “dieselome” analysis also showed that after a diesel transplant from a sick vehicle, the microbes in the previously healthy, efficient vehicle become more like those from the sick donor.

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Gordon concluded by saying:

“It is clear to us that the problem is not actually in software but it is in the microbes in the vehicles. Somehow the microbes in the vehicles that were failing the test were different than in the healthy vehicles.”

This reporter then asked Gordon if they had any explanation for what could have caused the difference. She responded:

We are unsure of the causes. But we believe the most likely explanation is excessive use of antimicrobial cleansers in the cleaning of vehicles, or possible the choice of air filtration systems that may have eliminated beneficial microbes from the vehicles. We are investigating.

Breakthrough method in microbial ecology: fMRI analysis of ordination plots.

As anyone who has read a recent article on microbial ecology knows, the name of the game is ordination plots. Looking for post-hoc patterns in 16S and metagenomics surveys is pretty much par for the course. Depending on your question and statistical inclinations there are a huge variety of ordination plots to choose from; NMDS, PCA, PCOA… not to mention the distance metrics; UniFrac (weighted or unweighted), Bray-Curtis, Jaccard, etc. One approach is to simply run all these analyses (QIIME does this by default) and then to look for patterns.

journal.pone_.0081330.g004-1024x367.png

But how to choose? If one plot shows a pattern and another shows a different pattern, how is a researcher to decide? Statistics is one possible approach, but we all know what Mark Twain said about statistics.

Better than statistics, is a new approach described in this week’s issue of QIIME THERAPY. In “fMRI analysis of ordination plots”, the authors describe a breakthrough approach for rapid and accurate classification of ordination plots for microbial ecology. Instead of arbitrary statistics, the researchers harbor the power of the unconscious human mind. Any human can look at a series of dots and see patterns but computers struggle with this simple task. Ask a 5-year old what shapes they see in an ordination plot and they’ll have ideas. But, as the authors describe, there are problems when scientists are involved… they tend to overthink the process and focus on irrelevant details like axis labels (meaningless in a PCA plot for example). In this work, the researchers circumvent the conscious brain by placing subjects in an fMRI machine and passing images of ordination plots through their field of vision. Patterns are classified on the basis of the strength of the reaction to the image. The authors show that this method is 93% accurate on mock community data and also unveiled patterns in tests data sets that had been missed by statisticians. In addition, this method takes 10% of the time and requires about 25% of the cost of a statistical analysis.

As a proof of principle, the authors applied this methodology to previously analyzed data from the Human Microbiome Project. While generally supporting previous conclusions, the authors also found that weighted UniFrac analysis suggested a novel correlation between the microbiome of the Hallux (big toe) and the microbiome of the non-dominant hand of participants. They plan further research to understand the causality of this connection.

The REAL Ghost-tree

Renowned parapsychologists Venkman, Stantz, Spengler and Zeddemore recently sat down with us to talk about their reactions to the newly released pre-print, “Ghost-tree: creating hybrid-gene phylogenetic trees for diversity analyses”.

“Initially we were really intrigued,” said Dr. Venkman, “We thought that finally someone had paid attention to what our field really needed!”

However, it quickly became apparent to the parapsychologists that the paper wasn’t what it seemed.

“The farther I got in the paper, the more it became apparent that the authors had no real grasp of apparitional experiences and the science involved in studying them,” said Dr. Spengler, “It was as if the authors were from a field that was antithesis to the field of parapsychology.”

I asked Dr. Spengler if he was familiar with the field of mycology.

“Mycology… Never heard of it.”

At this point in the interview, I was increasingly curious as to what exactly the parapsychologists thought was wrong with the paper.

“Well, you see, it is lacking… in ghosts,” explained Dr. Stantz, “In fact, there are no ghosts in the entire paper! It is very misleading!”

I thought about pointing out that the word “ghost” actually appears several times in the pre-print (at least seventeen), but decided against it. Parapsychologists can be a little scary when they get worked up about a topic.

In fact, they got so worked up over the Ghost-tree paper that they decided to write their own paper titled, “The REAL Ghost-tree: a hybrid-media phylogenetic tree for diversity analyses in apparitional science”.

“In a way, that terrible Ghost-tree paper was actually a good thing for the field of apparational science,” said Dr. Venkman, “Now parapsychologists and citizen scientists everywhere can put their apparitional experiences into an evolutionary context.”

When asked if they had any comments that they would like related to the Ghost-tree authors, Dr. Zeddemore had the following to say,

“Next time, actually include ghosts.”

Destination PhD

I recently had the opportunity to sit in on an exit seminar for a PhD candidate in my department (there was free food). The student began the seminar by detailing the hardships that they had faced throughout the completion of their dissertation which included smelly undergrads, dry eraser makers running out of ink and finding funds to go abroad for their field seasons (a common enough issue).

Field site #1: Resort on an island in the Caribbean

Travel to exotic destinations was key to the students dissertation since the student believed that resorts in exotic locations would have different, more exotic, microbes when compared with basic hotels in non-exotic locals (all of central USA). Although, the student had no preliminary data or any concrete hypotheses, the broader impacts of investigating tourist destinations and finding potential microbial health risks was significant enough for the student to find just enough funding for the project (quite an amazing feat in this day and age). Funding was obtained from the 99% Foundation, a group founded by the middle class to study the lifestyles of the rich and famous.

Field site #2: Ski resort in Switzerland

During the exit seminar, the student also discussed what inspired the project:

“I wanted to perform research that really meant something and that would provide great insight for human health. I wanted my research to be able to help solve global problems like reversing climate change, curing cancer, and finding a real fountain of youth. However even more than that, I wanted to do some traveling and couldn’t afford it; I’d never been to the Maldives or Switzerland before and I really wanted to go. Plus, this meant I could do all my field research over spring break.”

The student’s dedication to science is just admirable.

4.-The-Hilton-Maldives-Resort-and-Spa.jpg — Field site #3: Underwater resort in the Maldives

The student spent the rest of the seminar detailing the results of this exotic resort microbial study. Surprisingly, there were a lot of microbes shared between exotic resorts and non-exotic hotels (lots of E. coli) and the student didn’t find anything of any real interest or importance (just a little bit of platypus DNA, note: not a microbe). However, the student believes this was likely due to the limited scope of the project. They were only able to get enough funds to visit four exotic resorts and did not due to time constraints (spring break is only a week long) to collect replicates. The student is currently looking for additional funding to expand the study to include additional resort locations (ex. LotR filming locations in New Zealand). The student is also interested in performing a time series at one of the resorts which would require the student to remain at the resort for a prolonged period of time – an extreme emotional and financial hardship. The student would also like to expand the project to include cruise ships.

Field site #4: Isolated resort in Jamaica

Listening to this student (and eating free cookies) made me really proud of my department and the exemplary research that is going on. This exit seminar stressed the importance of funding novel hypothesis-less research projects that have the potential to generate lots and lots of superfluous data and that focus on really interesting, but uninformative, locations. Best of luck to this student in their future endeavors! If you need any help sampling, let me know!

FITBIOTICS

As the World has successfully found the Fittest Man and Woman on Earth for many consecutive years through the notorious CrossFit Games, a secret fit-weapon has been revealed. Supplements companies have collected the fittest microbes on Earth to help the athletes through their journey of fitness. A secret supplements company, until now known only by high levels athletes, sells the fittest microbiome on Earth: FITBIOTICS Inc.

After years of work and countless microbial sampling, the company has finally achieve to gather ALL microbes from ALL the fittest athletes in ALL domains aiming to transfer the “Crème de la crème” of ALL microbiomes from these super athletes to anyone. Forget the barbells, kettle bells, dumbbells and all other training gear. The hours of endless running, burpees, air squats, pull-ups, and jump rope have ended. To achieve the level of fitness reached by the reigning Champs, you only need to include the α-FITBIOME in your daily shake and you will have the FITTEST MICROBIOME ON EARTH! To achieve maximal results, FITBIOTICS Inc. recommends that you also take a one-hour daily bath with one scoop of their α-FITBIOME. When tested on completely inactive people with poor eating habits, this treatment has been shown to help improve strength and endurance by 300%*. And to all readers greatly informed about the risks of DNA in food, don’t worry; this product definitively contains no DNA (http://www.washingtonpost.com/news/volokh-conspiracy/wp/2015/01/17/over-80-percent-of-americans-support-mandatory-labels-on-foods-containing-dna/).

You are dreaming of lifting 200 pounds, running a marathon, completing an ironman or deadlifting 2.5 times your bodyweight? Don’t wait any longer and run to your closest store to get your

α-FITBIOME from FITBIOTICS Inc.

*Only when combined with a radical change in nutrition and daily physical conditioning activities.

Secret microbiome forensic study reveals #deflategate culprit

Chicago. January 31, 2015.

I had the incredible luck to be on an assignment in the midwest this week visiting the lab of Jock Giblet, one of the world’s experts in the new and merging superfield of microbiome forensics. Giblet has been at the forefront of forward thinking on using foreheads and foreskins and other microbiome rich samples to do forensics. His lab has already been involved in hundreds of criminal investigations where microbial forensics was used to do important things like (1) show that microbes were on people involved in crimes (2) that analysis of microbes can be used to reveal who was last in a room (making a few assumptions like, you know who was in the room and what their microbes look like and who was not in the room) and (3) the microbes could be considered as possible instigators of various crimes.

Anyway – I was there to interview Giblet about his latest amazing work on the how microbiome analysis can be used to cheat at card games. But he was distracted by something. He called me into his spacious yet somehow very dark and depressing office and said “Can I let you in on a secret?” Of course I said yes. Alas, for him, he never said “Can this be off the record?” so I am reporting to you what I then found out, along with some secret recordings I made with my awesome Google Glass recording device.

Over the next 24 hours I witness Giblet and members of his microbiome lab then do a top secret microbiome driven analysis of the deflategate controversy. It was so exciting to be witness to this edge cutting research. Below is a description of what I witnessed.

1. Giblet and team travel to the airport to collect footballs from the NFL

Edward_Butch_OHares_Aircraft_on_display_at_ORD-1024x768.jpg — The footballs lined up waiting to be picked up

2. Giblet brings footballs back to the lab and also collect wan assortment of other materials for control experiments

Aerial of the Top Secret Lab where Dr. Giblet works

3. They then set up a microbiome analysis in their top secret lab with some key samples for testing and as part of the experiment

A football collected at halftime from the Patriots game

New, sterile examples of the suspected tampering tools

4. It was here that I was able to finally activate the video recording on my Google Glass. It only worked sporadically but I did get some video of the Giblet lab in action carrying out a microbiome forensic study. Basically, they used these really complicated secret sampling devices that came hidden in a tube:

And they used this to collect microbiomes from multiple sources including hands, the suspected deflation devices (before and after handling), and the balls before and after handling. Here is what I could get:

After doing some test samples the then got the footballs from the NFL that they had picked up at the airport and sampled them too. They also spent a lot of time on the phone discussing some sort of sampling of the hands of all employees of the Patriots and the other team. And while we were sampling the footballs someone showed up in the lab with a bag of more of these special sampling devices labelled with names of various people.

They then took all the special sampling devices and “got the fu#*(#@ DNA out of them, for sure”. It was exciting to watch.

5. Sequencing

The DNA from the sampling devices was then dripped into a small device that plugged into a laptop computer via a USB port. It looked a bit like a thumb drive. Dr. Giblet spent a lot of time looking at the screen, typing some stuff, and crying and cursing. He then said “Screw these minions. I am going back to the Illuminati” and he carried a box of samples out the door, cursing, in a strange accent. I am not sure how he was connected to the Illuminati but nevertheless, he returned eight hours later (I was getting really impatient, and hungry, sitting there waiting for him, still wearing my Google Glasses). And he looked happier. And he said “Booyah – we have data”.

He then explained to me how he had taken the DNA out of the microbes in the samples and did some special chemistry and got out a file with information that would help determine what microbes were in each sample.

6. Analysis

Dr. Giblet and two other people who seemed to be employees of his, then sat in front of an old IBM computer doing something. I am not sure but I think their names were Jane Jane and Sir Robert. Very interesting people I note. Anyway, the cursed a lot, typed a lot, kept talking about some sort of chime they kept hearing. These were smart people I think. But really secretive and talking in code all the time. In fact, they kept asking Sir Robert to do more code, though I note, I had no idea what he was saying anyway.

Nevertheless, after 10 more hours they finally woke me up (I had fallen asleep on the lab floor) and said “We have the answer.” And then they had me sit in front of a computer to look at some pictures. By this point my Google Glasses were really acting up. The best pics I could get are shown below.

Apparently these graphs showed that the culprit behind the NFL DeflateGate controversy was none other than Jock Giblet himself. That is, the samples from the Patriots’ footballs most resembled samples from Giblet’s hands. He swore to his friends and colleagues that it was not him and that he would never do something like that. But as they called 911 they said “Sorry Jock. We will miss you.”

Then they shuffled me out the door too. They never noticed the Google Glass, but I have been cut off from my sources so not sure what happened to Jock after he was taken away.

Bactopets(c)

There is growing evidence supporting that having pets in the home from a young age can have profound effects on our long-term health. Dozens of recent studies have linked the microbes associated with doggie and kitty cat friendly households to the health of a building’s occupants, including a significantly decreased risk of asthma, allergies, and an overall less resilient microbiome. With such knowledge, parents now face a predicament that is sure to tug on the heartstrings. Parents shouldn’t have to sacrifice the long-term health of their child just because they don’t have the time or money to care for a furry, four-legged, divine carrier of microbes. Now, they don’t have to!

Introducing Bactopets©, a collection of stuffed animals that have the same microbiome as the real animal! Forgo all of the cleaning, pooper-scoopering, and shredded furniture with the same benefits as having a real cat or dog. Bactopets© are inoculated with a Slo-Release Microbial Technology™ to insure maximal effectiveness. We made Bactopets© to be extremely soft and adorable so they are guaranteed to improve your child’s microbiome because your child will be unable to resist the urge to rub it in on their face, snuggle with it (good for maximal microbial respiratory entry), and possibly even suckle on it. Bactopets© are odorless so you can even sneak this as a gift to your child without your germophobic spouse finding out.

Collect them all!

BactoLab© reflects the microbiome of a Labrador retriever who has been swimming in a stagnant pond, rolled on an unidentifiable carcass, chewed on numerous neighborhood sticks, and sniffed dozens of doggie butts. BactoLab© is now available in brown, black, and golden colors.

BactoTabby© reflects the microbiome of a tabby cat who has hunted several mice and birds, dug in a dirty litter box, and explored the most cobwebbed corners of the neighborhood.

BactoPetPlus© is a deluxe version of the aforementioned products with the addition of real pet dander for even greater long-term health benefits.

BactoSpray© is an inoculated dog or cat microbe solution that you can simply spray on your child’s favorite stuffed animal and around your home. BactoSpray© is also available in a more discrete packaging under the guise of “probiotic” to blend in well with your germophobic spouse’s collect of kombucha and yogurt.

New Marketing Campaign by Apple

“An Apple a day keeps the doctor away” – Apple’s New Slogan

Apple has launched a new marketing campaign in an attempt to revitalize interest in their MacBook computers after a researcher found a virtually undetectable mac virus known as Thundercat that can effect Apple computers running OS X LabRat. This campaign involves inoculating Apple MacBook computers with the naturally occurring GMO free bacteria, Canislupis tonitrui, found on organic Red Cumulus strains of apples. Researchers studied a variety of microbes from a variety of apple types before discovering this bacteria which releases anti-viral compounds into its environment. Apple claims that inoculation with this apple microbe will help prevent MacBook infection by Thundercat and provide other benefits to computer health including longer battery life and decreased frequency of internet pop up ads. Apple also plans to sell this bacteria to current Apple users through a “patch” that you can stick on your computer. These patches will be available for order from the App store shortly.

What do you think of Apple’s new marketing campaign? Will you buy the new microbe “patch” to protect against the Thundercat virus?