Second Genome Solutions


Todd DeSantis is Second Genome Co-founder and Senior Director of Bioinformatics. Todd has 17 years of experience designing and implementing bioinformatics solutions for analyzing microbial community dynamics. At Lawrence Berkeley National Laboratory he led the development of novel microbiome assays and analysis pipelines as a Molecular Microbial Ecology Software Developer. He is the chief architect of Greengenes™, an international effort to catalog global microbial diversity that provides microbial ecologists with reference databases for DNA quality assessment, alignment and classification. Todd also served as an analyst for the NIH Human Microbiome Project and has published over 60 scientific papers. At Second Genome, he manages all informatics work including identifying and recruiting microbiome scientist leaders, integration of multi-omics pipelines, cloud deployment for big-data analytics, and therapeutic pathway discovery.

Microbiome Biomarker Discovery for Diagnostic and Therapeutic Applications

Todd DeSantis, Director of Bioinformatics, Second Genome, Inc.


Microbiome discovery efforts are underway in multiple disease areas.  Challenges exist in sample collection, processing, assay selection and bioinformatics.  Therefore heterogeneity exists in published findings for biomarkers.  Using the Amazon cloud and machine learning, sets of consistent biomarkers can be observed in biospecimens from diseased subjects that differentiate them from healthy controls.  The benefits of applying consistent assays with internal controls within each test will be discussed.  Since the same data collected for diagnostic discovery, also aids in therapeutic hypotheses generation, a platform that outputs both will be outlined.

Learning Objectives:
– Be able to list at least 2 disease areas where microbiome analyses are applied.
– Be able to list at least 2 sources of variation in biomarker discovery in microbiome analyses.
– Be able to identify the benefits of internal controls in evaluating assay value.

My comment: In the context of his excellent presentation at the Molecular Diagnostics virtual conference earlier today, Todd DeSantis linked an article he co-authored to everything currently known about biophysically constrained nutrient-dependent RNA-mediated cell type differentiation in all living genera.

See: The phylogenetic composition and structure of soil microbial communities shifts in response to elevated carbon dioxide


The results suggest that the richness, composition and structure of soil microbial communities shift in response to eCO2.

My comment: In the context of his presentation, Todd DeSantis also mentioned this article: The Western English Channel contains a persistent microbial seed bank


…the seed-bank hypothesis (Lennon and Jones, 2011) has implications for our understanding of ecological resilience and thresholds to change, especially the reversibility of threshold shifts (Groffman et al., 2006). This concept is elegantly described for marine ecosystems in the One Ocean Model for ecosystem biodiversity (O’dor et al., 2009), whereby microbial life over millions of years can diffuse through the whole ocean, creating a potential seed bank for rapid community adaptation to change. This theoretically enables the community to maintain equilibrium with changing environments, so that the community always prevails (O’dor et al., 2009).

My comment: Everything known about biophysically constrained marine ecosystems and terrestrial ecosystems links the sun’s anti-entropic virucidal biological energy to nutrient-dependent pheromone-controlled RNA-mediated cell type differentiation in all living genera, but also to weekend evolution of the bacterial flagellum. Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system

Facts that refute neo-Darwinian evolution (over millions of years) were the focus of my poster presentation today at the Molecular Diagnostics virtual conference.  It is available in the Poster Hall in the section with the title:  “New Approaches to Genomic Health.”  If neo-Darwian theory was the road to genomic health over millions of years, we would not see evidence of transgenerational epigenetic of the Zika virus manifested in craniofacial deformities and brain development. Weekend evolution of the bacterial flagellum and prevention of Zika virus damage can both be viewed int he context of what is known about biophysically constrained protein folding chemistry in all living genera.

What is life when it is not protected from virus-driven entropy


The anti-entropic force of virucidal ultraviolet light (UV) links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair. In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans. Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry. Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.

My comment: More than 20,000 people have already viewed the details about free event, and more than 100 have already shared the details.

I mention this because Todd DeSantis graciously answered my question about the role of the innate immune system. In my model, it links the de novo creation of nutrient-dependent olfactory receptor genes to the biophysically constrained chemistry of RNA-mediated cell type differentiation in all living genera from microbes to human. Even though Todd DeSantis was not familiar with my claim about the link from the microRNAome to the gut microbiome, he seems to be somewhat sure that the innate immune system is the mediator of biologically-based cause and effect.

That suggests my past claims about the links from marine ecosystems and terrestrial ecosystems include 1) what was known to Einstein about math and physics; 2) what was known to Schrodinger about the anti-entropic energy of sunlight, and 3) what was known to Dobzhansky about amino acid substitutions and the biodiversity of morphological and behavioral phenotypes in all genera.

The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression

Sperm is epigenetically programmed to regulate gene transcription in embryos

Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

The link from the anti-entropic energy of sunlight to the physiology and reproduction of soil bacteria and/or marine bacteria extends from the nutrient-dependent pheromone-controlled RNA-mediated cell type differentiation in all living genera via the conserved molecular mechanisms we detailed in the context of our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior

See our section on molecular epigenetics:


Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

See for comparison:

“I never meant to impugn the rationality of science.” — Thomas Kuhn, author of The Structure of Scientific Revolutions

Epigenetics: It doesn’t mean what quacks think it means


The first brand of cranks to abuse epigenetics were, not surprisingly, creationists. In epigenetics and the observation that there are traits that are heritable that do not directly depend on the primary DNA sequence they saw what they thought was a “fatal flaw” in Darwin’s theory of evolution.

My comment: The creationists appear to have been the first to link virus-driven energy theft to all pathology after also being among the first to link nutritional epigenetics from the Precision Medicine Initiative to healthy longevity via everything currently known to serious scientists about biophysically constrained RNA-mediated amino acid substitutions and biodiversity.

Viral Genome Junk Is Bunk

So, where do viruses come from that essentially share the same sequences as those found in their host genomes? Perhaps the evolutionists have placed the cart before the horse on this issue, as proposed by several creationist scientists.4,6 In fact, in an ironic twist, the evidence mentioned above indicates that viruses likely arose from their hosts and not the other way around. As molecular biologist and biochemist Peter Borger notes, “The most parsimonious answer is: the RNA viruses got their genes from their hosts.”6

See also: Regulatory evolution of innate immunity through co-option of endogenous retroviruses


We speculate that the prevalence of IFN-inducible enhancers in the LTRs of these ancient retroviruses is not coincidental, but may reflect former viral adaptations to exploit immune signaling pathways promoting viral transcription and replication (32).

My comment: Speculation about regulatory evolution of innate immunity ends with recognition of the fact that innate means the immunity existed before it was required to protect organized genomes from virus-driven entropy. If innate immunity required the co-option of endogenous retroviruses, supercoiled DNA would not be required to prevent virus-driven energy theft from leading to all pathology.

Role of olfaction in Octopus vulgaris reproduction.

Future work on O. vulgaris olfaction must also consider how animals acquire the odours detected by the olfactory organ and what kind of odour the olfactory organ perceives. The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000).

My comment: Serious scientists have arrived at the point where marine ecology and terrestrial ecology link microbes to humans via conserved molecular epigenetics — and neo-Darwinists are still touting pseudoscientific nonsense. I wonder how many more examples of the beneficial virucidal effects of the sun will be required before neo-Darwinian theorists quit claiming there are beneficial mutations on land or in the sea.

Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort

Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia


The presence of viral nucleic acid at sites of pathology in brain and liver together with the observation that virus propagated in cell culture is capable of inducing disease in naive fish implicates TiLV as the causative agent of outbreaks of both viral encephalitis and syncytial hepatitis in tilapiines in Israel and Ecuador. The fact that TiLV has been detected in association with disease in two geographically disparate sites underscores thatTiLVposes a global threat to tilapiine aquaculture. We have no evidence that TiLV can infect other species; however, the genetic dissimilarity of TiLV to other viruses suggests the potential for discovery of related viruses as TiLV sequences are employed for phylogenetic analysis.

My comment: I know how the de novo creation of nucleic acids is linked to RNA-mediated nutrient-dependent healthy longevity via the physiology of reproduction. I do not know how viral nucleic acids or virus-driven energy theft and mutations are linked to anything except pathology.

Also, I do not know how neo-Darwinian theorists could not recognize that the link from the Ebola viruses in West Africa and the Zika virus in Brazil can be compared to the link between the tilapia viruses found in Israel and in Ecuador. Unless they find some bats or mosquitoes that can fly for long distances under water it does not seem likely that their claims about evolved viruses can continue to hold water. Viruses adapt by stealing energy from their hosts. Viruses don’t evolve, and their hosts either adapt to the threat of the viruses or become part of the fossil record.

See also:

A lesson from wheat evolution: From the wild to our spaghetti dish


The authors have now shown that the initial domestication of emmer wheat involved a reduction in unsaturated fatty acids and the secondary domestication of durum wheat from emmer wheat involved changes in amino acid content.

Stone Age humans brought deer to Scottish islands by sea: study” 


“Our results imply that Neolithic humans were transporting deer considerable distances, by sea, from an unknown source” some 4,500-5,500 years ago, co-author David Stanton of Cardiff University told AFP by email.

“These results are surprising… The evidence suggests that we have misunderstood our relationship with this species,” he added.

My comment: Does anyone who is not a neo-Darwinian theorist believe that the amino acid content of wheat or grasses and other plant life is not linked from the physiology of nutrient-dependent pheromone-controlled reproduction in soil microbes to the microRNAomes of mammals, such as deer? Does anyone  who is not a neo-Darwinian theorist believe that Neolithic humans were transporting deer by sea 4,500-5,500 years ago?



Keep Reading