New Applications for Next Generation Sequencing!!!

While getting ready for work this morning I was thinking about exciting application areas for NGS technologies.

What about the personal sequencing of fecal matter to determine the composition and species of bacteria in a person's own stool? This test could be done routinely for monitoring and could generate a serious amount of revenue. Each poop is an opportunity for NGS!

What do you think?

1. Colorectal cancer: given

1. Colorectal cancer:
given that at the vast majority of stool DNA is bacterial and the vast majority of human DNA in stool DNA is from healthy cells and not the tumours you're going to have to a do a massive amount of sequencing to have any chance of seeing any tumour sequence. Target capture could improve this but it's never going to be as cheap as Exact Sciences of Epigenomics tests.

2. Ulcerative colitis:
Cause is currently unknown, so you'll first have to determince the cause before you can develop a diagnostic - no mean feat.

3. Pseudomembranous colitis:
may be possible but is it going to be any better or cheaper than the immunoassay for C.difficile toxin.

4. Diverticulitis:
Unknown cause. You may be able to detect a bacterial infection as a symptom but it would be difficult to use that to diagnose diverticulitis over other causes of infection.

5. Irritable bowel syndrome:
Again, unknown cause. As we've seen, a bacterial overgrowth may be associated with up to 33% of IBS cases but you'll struggle to get reimbursement for a test with such a low detection rate.

My company will use

My company will use sequencing to diagnose the following five conditions:

1. Colorectal cancer
2. Ulcerative colitis
3. Pseudomembranous colitis
4. Diverticulitis
5. Irritable bowel syndrome

There are other disorders of the large intestine and rectum which I'll likely add to the menu but this represents my current thinking.

"I'm in the process of

"I'm in the process of seeking VC funding to start a diagnostics company focused on the sequencing of stool samples. People may joke about the application but it has enormous revenue potential. I'm willing to risk everything I've earned to pursue this opportunity. You will all regret making fun on me!!!"

Fill us in on the details - what are you going to diagnose? how much will it cost per test? what is your patient pool? who has agreed to reimburse the test?.....

I'm in the process of seeking

I'm in the process of seeking VC funding to start a diagnostics company focused on the sequencing of stool samples. People may joke about the application but it has enormous revenue potential. I'm willing to risk everything I've earned to pursue this opportunity. You will all regret making fun on me!!!

My poop gets dark black in

My poop gets dark black in color when I eat chocolate.

What ever happened to the

What ever happened to the person who had a colonoscopy because of the blood in their stool? Did the test come up negative?

Sequencing can help you

Sequencing can help you figure out which types of bacteria are in your poop.

How long has your poop

How long has your poop smelled like fish?

My poop smells like fish but

My poop smells like fish but I don't eat any seafood. Why does this happen?

Yes, my poop also gets very

Yes, my poop also gets very wet when low on protein. Having a glass of milk or some yogurt can help to make your poop more solid.

Sometimes my poop is very

Sometimes my poop is very soft, wet, and messy as well. Usually, this is a sign of low protein in my diet. I would recommend taking a look at your diet to see if it is low in protein.

I've been having serious

I've been having serious problems with my bowels for the last month and I don't understand why my stool is no longer solid. My stool isn't as wet as diarrhea but it isn't solid. Sort of like mud in consistency which is closer to diarrhea. I turned 60 years of age a few months back and don't know if this has anything to due with getting older. It is very messy when I go to the bathroom and feel I may have a bacterial problem. What test is best for this situation? Has anyone experienced this type of problem with their own stool? It also smells very bad.

if only a third of those with

if only a third of those with IBS have an associated bacterial overgrowth any test aimed at this as a marker will only ever diagnose a third of IBS sufferers.

What you are missing is the

What you are missing is the point! With NGS the detection rate and accuracy will improve over a simple bacterial overgrowth assay. NGS is more powerful and this is what will lead to revenue and a new standard of care for IBS.

so you're proposing a

so you're proposing a diagnostic with just a 33% detection rate, 10% false positive rate, costing over $1,000 a test and you're expecting to make $250million......I won't be investing!

"In the future please do a

"In the future please do a bit more research before making your bold uneducated claims"

your paper, like the NIH web-page, says that bacterial growth is 'connected' to IBS, not 'THE cause'. Here's a quote from your link:

" In patients with IBS, more than a third also were diagnosed with small intestine bacterial overgrowth, compared to fewer than 10 percent of those without the disorder"

So, 33% of people with IBS have the bacterial overgrowth, 10% of healthy people have bacterial overgrowth AND 67% of people with IBS DON'T have bacterial overgrowth. A link yes, but hardly a definitive diagnostic. And enough with the insults - it doesn't strengthen your point.

An overgrowth of bacteria in

An overgrowth of bacteria in the gut has been definitively linked to Irritable Bowel Syndrome in the results of a new Cedars-Sinai study which used cultures from the small intestine. This is the first study to use this "gold standard" method of connecting bacteria to the cause of the disease that affects an estimated 30 million people in the United States.

http://www.sciencedaily.com/releases/2012/05/120525103354.htm

Below is a reference to paper which you should read.
Gene Kim, Fnu Deepinder, Walter Morales, Laura Hwang, Stacy Weitsman, Christopher Chang, Robert Gunsalus, Mark Pimentel. Methanobrevibacter smithii Is the Predominant Methanogen in Patients with Constipation-Predominant IBS and Methane on Breath. Digestive Diseases and Sciences, 2012; DOI: 10.1007/s10620-012-2197-1

In the future please do a bit more research before making your bold uneducated claims.

And I bet your pants now fit

And I bet your pants now fit better!

"|You need to be educated so

"|You need to be educated so I will keep it simple so you can understand.

IBS is caused by bacteria in the large intestine. Bacteria contain DNA. DNA can be sequenced"

no it's not, the cause is currently unknown. This is from the NIH:

http://digestive.niddk.nih.gov/ddiseases/pubs/ibs/

and here's a quote from the above NIH web-page

"The causes of IBS are not well understood. Researchers believe a combination of physical and mental health problems can lead to IBS. The possible causes of IBS include the following..."

You're very long on the insults but very short on substance.

"the cause of IBS is unknown,

"the cause of IBS is unknown, so how will sequencing stool samples diagnose it?"

You need to be educated so I will keep it simple so you can understand.

IBS is caused by bacteria in the large intestine. Bacteria contain DNA. DNA can be sequenced.

the cause of IBS is unknown,

the cause of IBS is unknown, so how will sequencing stool samples diagnose it?

"good luck with that......but

"good luck with that......but you might want to come up with a condition you can diagnose before giving up your day job."

No problem, Irritable Bowel Syndrome (IBS) is one condition we can diagnose today!! Geeze, you might want to give up your day job just to do some research or get an education.

"After thorough analysis I've

"After thorough analysis I've come to the conclusion that the sequencing of stool samples represents a $250 million dollar market opportunity. There is obviously great clinical utility in the sequencing of microbial biomes within the GI tract to diagnose disease."

good luck with that......but you might want to come up with a condition you can diagnose before giving up your day job.

After thorough analysis I've

After thorough analysis I've come to the conclusion that the sequencing of stool samples represents a $250 million dollar market opportunity. There is obviously great clinical utility in the sequencing of microbial biomes within the GI tract to diagnose disease.

Sadly, Exact Sciences seems

Sadly, Exact Sciences seems to be going down that path with gusto.

Don't know about hairball

Don't know about hairball analysis, but cat hair STR multiplexes are out there for forensic analysis of cat hair. Does that help?

Just because you can sequence

Just because you can sequence it doesn't mean you should sequence it!

Don't let Lucifer hear you say that!

Here is the take home

Here is the take home message....

Just because you can sequence it doesn't mean you should sequence it!

Nuff said...

The size of your dumps is

The size of your dumps is directly correlated to the amount of food you eat. You don't need sequencing to tell you why some dumps are big, just monitor how much food you eat.

"My cat coughs up hairballs.

"My cat coughs up hairballs. Is there a good market for hairball analysis?"

No, this is completely normal for felines. Also, your cat might be licking itself too often which can increase the frequency of hairballs. Let's please keep the replies on this post to the important topic of poop.

Now, that is completely

Now, that is completely ridiculous! There is no DNA in farts to sequence. The preferred starting material when suffering from GI tract issues is stool. The person who suggested the sequencing of farts is not very smart. Pee and poo make perfect sense for sequencing and represent enormous clinical value.

How about sequencing farts?

How about sequencing farts? Or would that be better done by mass spectrometry? Or better yet, GC/MS.

My cat coughs up hairballs.

My cat coughs up hairballs. Is there a good market for hairball analysis?

Sequencing your Pee Pee would

Sequencing your Pee Pee would also be helpful. As would sequencing a juicy green lunger.

NGS has utility in discovery

NGS has utility in discovery and development of diagnostics but there's little chance that NGS will make it in to any clinical lab as a routine diagnostic tool any time soon. Even with costs coming down it's never going to be as cheap as an ELISA or PCR so reimbursement by payers will not happen.

I'm thinking about starting a

I'm thinking about starting a new company called "Craplete Genomics" which will specialize in offering whole genome sequencing of bacteria from poop. What do you think, is the market ready?

High throughput sequencing

High throughput sequencing offers enormous clinical value. There isn't a more powerful technology available today. I'm convinced the sequencing of poop is not a craopy idea. Great post!

Reminds me of the

Reminds me of the self-proclaimed "experts" declaring that there would be no clinical utility for Sanger...

"There are many publications

"There are many publications illustrating the clinical utility of sequencing for stool samples.

Read the one below to educate yourself...

http://wwwnc.cdc.gov/eid/article/14/11/pdfs/08-0589.pdf"

There are much easier and cheaper ways of diagnosing campylobacter food poisoning than NGS

quoted from the conclusion of

quoted from the conclusion of the paper you link to:

"Therefore, high-throughput DNA sequencing may soon be adopted as the main method for examining microorganisms in major clinical laboratories"

"MAY soon" as in "not currently". The study in the paper is based on the illness of ONE man.

There are many publications

There are many publications illustrating the clinical utility of sequencing for stool samples.

Read the one below to educate yourself...

http://wwwnc.cdc.gov/eid/article/14/11/pdfs/08-0589.pdf

Dr. Khoruts and his

Dr. Khoruts and his colleagues have carried out 15 more fecal transplants, 13 of which cured their patients.....
“In terms of hard-boiled science, we’re falling short of the mark,” he said. A better picture of the microbiome will only emerge once scientists can use the genetic information Dr. Weinstock and his colleagues are gathering to run many more experiments.

the above are quotes from your article. only 13 patients treated - I'd call that a niche application (which along with oncology is what I said it would be used for). And the authors themselves say "in terms of hard-boiled science we are falling short of the mark" and admit themselves that they cannot use the genetic information they get from sequencing. The treatment was an experiment in replacing the gut flora and fauna and was not done on the basis of sequencing as confirmed by this quote from the article you link to
"Instead of a crude transplant, Dr. Khoruts hopes that eventually he can give his patients what he jokingly calls “God’s probiotic”
ie he hopes EVENTUALLY that sequencing will allow the diagnosis and treatment - the article clearly states it's not there yet. You should read the articles you quote before posting unless you are proud to flaunt your stupidity

I challenge you to give one

I challenge you to give one example of a treatment being given based on NGS of stool samples. Your vague statement above is marketing bullshit spouted by NGS suppliers about the 'future potential' of NGS in clinical diagnostics. In reality, for anything other than oncology or niche applications, use of NGS for diagnostics or personalized medicine is decades away at best. The same hype was applied to arrays in the late 90's but it never materialised....

Took me all of ten seconds to find this....if you want me to delve into PubMed, no prob. DO your research before, unless you are proud to flaunt your stupidity...

http://www.nytimes.com/2010/07/13/science/13micro.html?pagewanted=all&_r=0

"The NIH Human Microbiome

"The NIH Human Microbiome Project is actively sequencing stool samples.

Below is a link to this HIH project which clearly articulates the value in sequencing stool.

http://hmpdacc.org/micro_analysis/microbiome_analyses.php

Next time do some online research before posting your inaccurate beliefs."

The link you give is to basic research - the challenge was to name a treatment that had been given on the basis of sequencing stool samples.
Here's the mission statement for the work:
"The HMP is performing 16S rRNA and metagenomic sequencing of samples from a healthy human population to address questions such as whether there is a "core" microbiome at individual body sites and whether variation in the microbiome can be systematically studied."
The emphasis on "whether variation in the microbiome CAN BE systematically STUDIED" not even an attempt to assign a clinical use.
Next time read the question before posting your inaccurate responses. Similar basic research was done with arrays and claims were made for the healthcare benefits it would bring but nothing has yet materialised.

The NIH Human Microbiome

The NIH Human Microbiome Project is actively sequencing stool samples.

Below is a link to this HIH project which clearly articulates the value in sequencing stool.

http://hmpdacc.org/micro_analysis/microbiome_analyses.php

Next time do some online research before posting your inaccurate beliefs.

"Sequencing your stool sample

"Sequencing your stool sample will add a lot of additional information about your health profile. The bacteria in our large intestine play an important role towards our well being and sequencing your still will provide a complete picture of your individual health and well being. It is worth every penny"

I challenge you to give one example of a treatment being given based on NGS of stool samples. Your vague statement above is marketing bullshit spouted by NGS suppliers about the 'future potential' of NGS in clinical diagnostics. In reality, for anything other than oncology or niche applications, use of NGS for diagnostics or personalized medicine is decades away at best. The same hype was applied to arrays in the late 90's but it never materialised....

Just because everyone loves

Just because everyone loves to talk about NGS doesn't mean it can solve all the world's health problems. I feel bad for the person who has excessive diarrhea but sequencing is unlikely to help. There is also little value in sequencing poop. This post is very funny, except for the guy with colon cancer, but let's please stop thinking NGS can do everything. Poop belongs in the toilet not in a sequencer.

I don't think my diarrhea is

I don't think my diarrhea is due to diet. I'm willing to do any sort of testing to figure out what is wrong. I poop in my pants on the way to work and it is negatively affecting my life.

I don't believe sequencing of

I don't believe sequencing of your diarrhea will be helpful, it likely ha something to do with your diet.

I've been suffering from

I've been suffering from excessive diarrhea over the last few months and I don't know why. Would sequencing of my diarrhea be informative?

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