HMP: The Bugs Selected for Sequencing

Dear Friends,

The collection of human and microbial cells in our body produce a vast milieu of proteins through their collective genomes. These proteins function as 3-D structures that are either neutral, beneficial or harmful to us. As we look into their functioning in our body, how they combine to make the many necessary and beneficial pathways and structures, we will also see ways in which certain pathogenic proteins hamper, inhibit or destroy pathways and structures, causing our body to malfunction — effecting our long term survival—bringing the de-evolutionary hypothesis into reality.

Let’s look at what bugs are presently being sequenced or are targeted to be sequences by the Human Microbiome Project (HMP) as members of the selected group of microbes to be called the reference genomes. They were chosen by a broad consensus of scientists worldwide because they are thought to be the most likely residents of the microbiomes of the gastrointestinal tract, skin, nasal, oral, urogenital and airways. Here are the questions I will address in the coming emails:

1. What are the bugs that have been selected for full genomic sequencing—to be members of the Reference Genome?

2. What is the evidence of their symbiotic relationships with our human cells, tissues and systems—specifically what pathways, receptors, enzymes and structures do they help facilitate?

3. What is the evidence demonstrating that certain pathogens in our microbiome weaken our health and vitality? And how do they lead us down the proverbial de-evolutionary path?

Lets take a look at how the HMP answers these questions.

Reference Genomes of the Human Microbiome Project:

In order to facilitate the phylogenetic and functional analysis of the metagenomic sequences produced from human body sites, the HMP plans to sequence, or collect from publicly available sources, a total of 1000 reference genomes. The organisms included in this collection have all been isolated from a human body site. The information gained from the Reference Genomes will allow 16S RNA sequences and metagenomic sequence from uncharacterized microbiome organisms to be grouped phylogenetically with related organisms from the reference set providing information about the taxonomy of the unknown strains. Likewise, functional characterization of proteins in the reference organisms will aid in the functional annotation of related proteins contained in the sequence fragments derived from metagenomic samples.

I have discussed the issue of taxonomy many times with you individually, in classroom lectures, and in this newsletter. So far, the commercial probiotic industry has not gone through the universal scientific process of nomenclature, as all other biological sciences have done since the age of Aristotle. Almost all companies have named their species, and most certainly their subspecies, with propriety designations, to protect their “intellectual property”. This type of behavior thwarts of whole scientific process of discovery. We don’t know what bugs we are actually buying as consumers, since these organisms are not recognized with the universal scientific name, such as ATCC and other international repositories provide. As of this date, claims about organisms, are just that—in-house claims. The commercial industry needs to join the efforts of HMP and allow their organisms to go through the universal typing procedure—and get universal designations for their organisms. As you know, I have much passion for this field, and strongly believe that science needs to come first, before any commercial venture occurs.

The HMP has developed a detailed set of guidelines for inclusion of a strain in the reference genome group. They also welcome suggestions for inclusion of strains yet under consideration from groups outside their own.

The strain selection criteria that the Genome Centers are proposing to sequence are:

• Phylogeny and uniqueness of the species– It is anticipated that the finishing or improvement of the genomes of species that represent novel lineages will enable broad representation of as many lineages as possible, regardless of other criteria, and will provide improved scaffolding for the metagenomic data that are being produced. These genomes will also provide valuable information to groups beyond those involved in metagenomics studies.
• Established clinical significance– From the initial work with the sub-working groups, as well as from other sources and literature on the individual strains, we do have knowledge on relevance to health or disease states. We believe that any strain that has an established clinical significance to some health or disease condition should be included in the subset proposed to receive some level of improvement.
• Abundance (dominance ) in a body site– Similarly, some strains have accompanying information on abundance and relative abundance in the various body sites. We believe that any strains that have established information on abundance in a body site should be included in the subset proposed to receive some level of improvement. Additional reasoning for these isolates include: (a) the more predominant organisms will contribute the largest number of shotgun read and thus should be sequenced to aid in identifying these reads; (b) the more prevalent organisms will most likely have a bigger impact on metabolic capabilities of the community and thus one would want to know their metabolic pathways. This can only be obtained by complete genome sequences or finished genomes.
• Duplicate species but found in different body sites– For obvious reasons, duplicate species present an interesting data set that might have different metabolic capabilities dependent on which body sites they are found. For example on the strain Master List we currently have isolates of Gardnerella vaginalis that have been collected from vagina as well as skin.
• Opportunity to explore pan-genomes– Again, isolates that have already been closed by other genome sequencing efforts outside of the HMP may be from other environmental niches, and by having additional closed isolates we can obtain more information on the associated pan-genomes. For example, we are all aware of the extra Megabase of DNA obtained when the genome of E. coli 0157 was compared to E. coli K12 as the finished reference genome.
• Poor quality draft assembly that needs some improvement– In situations where a genome did not assemble well.
• Other– In situations where there is some criteria other than those justifications listed above.

The Genome Sequencing Centers for the HMP are located at The Broad Institute (of MIT and Harvard, Washington University, Baylor College of Medicine- Human Genome Sequencing Center (BCM-HGSC) and J. Craig Venter Institute.

The percent breakdown of numbers of bacterial species to be sequenced and their respective ecological niches are: GI tract- 27% (count-307), Oral- 23% (count-269), Skin- 19% (count-220), Urogenital tract-18% (210), Airways- 12% (count-138), Blood-1% (count-7), Heart- 0% (count- 1) and Eye- 0% (count-1).

Next week we will zero in on some of the GI tract selected species and the specifics of their genomic ability enabling their proteomic contribution to the overall functioning of our body. Exciting isn’t it!

Sincerely yours,

Seann Bardell

BioImmersion.com

Clinical Note:

In our two previous newsletters we have been looking at the two grouping of our synbiotic formulas—the American collection of bugs (in Oct. 7th email/newsletter) and their therapeutic food mix, and the last week the Bulgarian collection. All of our probiotics have gone through the toxonomy process.

As you can see in the picture below we have seven products left to discuss—let’s go over the four on the right. I classify these as our Oxidative Stress Reducing therapeutic foods—foods that clearly support the body’s Antioxidant Defense System.

On the far right we have Cruciferous Sprouts, and to their left we have wild blueberries —endogenous antioxidant support and exogenous antioxidant support respectively.

Cruciferous Sprouts Complex (powder) and the Cruciferous Sprouts Complex (capsules) have a slightly different profile of cruciferous sprouts (click on the links to see). The capsuled product was made for those individuals who don’t like the taste of cruciferous.

How to use and remember: Take one teaspoon or four capsules daily to enhance P2P production in every cell in the body. The glucosynolate family of molecules within this product trigger not just liver cells but all cells DNA to transcribe the production of the phase II enzymes (P2Ps) and therefore you are enhancing the body’s own ability to produce certain proteins that counteract inflammation, oxidation and that are crucial for detoxification. This ability we term endogenous Antioxidant Defense System support.

Wild Blueberry Daily and Wild Blueberry Extract were created to bring in the antioxidant, anti-inflammatory and neuro-regenerative power of the blueberry into our bodies to reduce oxidative stress. Clinical trails have clearly demonstrated the blueberry’s ability to enhance brain function—protecting it from oxidation. The same can be said for its protective benefits within our GI tract. The key portion of the blueberry providing these benefits are contain within its polyphenols—found within their purple pigment; and, is the reason we extracted the pigment to create the Wild Blueberry Extract. Additionally, we selected the Nova Scotia Wild Blueberry because it was rated by our USDA as the number one berry in North America for its oxygen radical absorbent capacity (ORAC).

How to use and remember: It takes us ¾ of a cup of blueberry to fill one capsule of the Daily. It’s ORAC score per capsule is 2000. It takes 1 and ¼ cup so to fill one capsule of the Wild Blueberry Extract whose ORAC score is 4000 per capsule. Use the Daily for prevention and the Extract for correction.

The Last Quiz Answer: The inner world of caves—beneath our feet are countless miles of cave passages with caves deep enough to engulf the Empire State Building. They are the least explored passes on earth and life abounds in this subterranian world. Here lives some of the strangest and least known animals on the planet. This amazing creature was filmed by the Planet Earth team. Frankly, I don’t know what it is. Perhaps some sort of blind salamander with radar like antenna. What do you think? Happy Halloween!

The amazing work in molecular biology keeps unfolding: 3-D Structure Of Human Genome: Factal Globule Architecture Packs Two Meters Of DNA Into Each Cell. This comes from the Broad Institute—one of the four sequencing centers used for the Human Microbiome Project.