Background: Microbiome biomarker discovery for patient diagnosis, prognosis, and risk evaluation is attracting broad interest. Selected groups of microbial features provide signatures that characterize host disease states such as cancer or cardio-metabolic diseases. Yet, the current predictive models stemming from machine learning still behave as black boxes and seldom generalize well. Their interpretation is challenging for physicians and biologists, which makes them difficult to trust and use routinely in the physician-patient decision-making process. Novel methods that provide interpretability and biological insight (...) are needed. Here, we introduce "predomics", an original machine learning approach inspired by microbial ecosystem interactions that is tailored for metagenomics data. It discovers accurate predictive signatures and provides unprecedented interpretability. The decision provided by the predictive model is based on a simple, yet powerful score computed by adding, subtracting, or dividing cumulative abundance of microbiome measurements. -/- Results: Tested on >100 datasets, we demonstrate that predomics models are simple and highly interpretable. Even with such simplicity, they are at least as accurate as state-of-the-art methods. The family of best models, discovered during the learning process, offers the ability to distil biological information and to decipher the predictability signatures of the studied condition. In a proof-of-concept experiment, we successfully predicted body corpulence and metabolic improvement after bariatric surgery using pre-surgery microbiome data. -/- Conclusions: Predomics is a new algorithm that helps in providing reliable and trustworthy diagnostic decisions in the microbiome field. Predomics is in accord with societal and legal requirements that plead for an explainable artificial intelligence approach in the medical field. (shrink)

Research on the human microbiome has gen- erated a staggering amount of sequence data, revealing variation in microbial diversity at the community, species (or phylotype), and genomic levels. In order to make this complexity more manageable and easier to interpret, new units—the metagenome, core microbiome, and entero- type—have been introduced in the scientific literature. Here, I argue that analytical tools and exploratory statisti- cal methods, coupled with a translational imperative, are the primary drivers of this new ontology. By reducing the (...) dimensionality of variation in the human microbiome, these new units render it more tractable and easier to interpret, and hence serve an important heuristic role. Nonetheless, there are several reasons to be cautious about these new categories prematurely ‘‘hardening’’ into natural units: a lack of constraints on what can be sequenced metagenomically, freedom of choice in taxonomic level in defining a ‘‘core microbiome,’’ typological framing of some of the concepts, and possible reification of statistical constructs. Finally, lessons from the Human Genome Project have led to a translational imperative: a drive to derive results from the exploration of microbiome variation that can help to articulate the emerging paradigm of per- sonalized genomic medicine (PGM). There is a tension between the typologizing inherent in much of this research and the personal in PGM. (shrink)

*Presented at the Western Canadian Philosophical Association Conference 2019 at the University of Lethbridge in Lethbridge, Alberta.* -/- This paper discusses some issues that arise when applying structural realism to biology. I begin by reviewing Katherine Brading’s version of structural realism with a hierarchy with proliferation of models.1 I then attempt to apply Brading’s structural realism to a biological example. This biological example suggests an issue with the use of shared structure. In response, I suggest the use of relevant relations (...) instead of shared structure. I then discuss Steven French’s use of eliminativist ontic structural realism in biology. Additionally, I consider John Dupré and Maureen A. O’Malley’s discussion of metagenomics and claim that biological entities are better described as self-sustaining biological processes.2 These metagenomic insights suggest an eliminativist view is preferable in biology. I conclude with an attempt to combine Brading’s and French’s approaches into an eliminativist relevant relationalism that retains the structuralist flavor and is applicable to the fluid, constantly changing entities found in biology. -/- 1. Katherine Brading, “Structuralist Approaches to Physics: Objects, Models and Modality,” chap. 3 in Scientific Structuralism, ed. Alisa Bokulich and Peter Bokulich, vol. 281, Boston Studies in the Philosophy of Science (Dordrecht: Springer Netherlands, 2011), 43–65, isbn: 9789048195978, doi:10.1007/978-90-481-9597-8_3. 2. John Dupré and Maureen A. O’Malley, “Metagenomics and biological ontology,” Studies in History and Philosophy of Biological and Biomedical Sciences 38 (2007): 84. (shrink)

Over the last three decades, studies in microbiology have exposed a world of diverse and dynamic interactions. Through metagenomic sequencing, complex bacterial communities became visible and proved important for many biological phenomena. As a result of discovering the connection between microorganisms and organisms’ survival, the notion of the holobiont has become prominent and has been suggested as a biological individual. The view of the holobiont as an individual, commonly known as the Hologenome Theory, focuses on the interactions and relations between (...) the host and its symbionts in the host’s development and evolution. Today, the holobiont is at the heart of the debate on the nature of the biological individual, a debate which is connected to the same question about the nature of the individual organism. (shrink)

RESUMO A alimentação é o fator que mais onera um sistema de produção animal. Assim, a utilização de diferentes estratégias de alimentação dos animais ainda é o grande desafio da nutrição animal, principalmente, levando em consideração as exigências nutricionais de diferentes categorias de ruminantes, em especial bovinos em regiões tropicais, haja vista que a sazonalidade na produção de forragens afeta diretamente a produção bovina, promovendo inadequação no atendimento das exigências nutricionais dos animais principalmente em minerais e vitaminas. Uma alimentação que (...) não atenda as exigências nutricionais dos ruminantes gera prejuízos no sistema de produção, além de, em casos mais graves, ocasionar a perda do animal. Estudos que abordam o efeito e a importância de vitaminas e minerais na nutrição bovina são escassos e necessários. Recentemente a National Research Council (NRC) apresentou novos registros das exigências nutricionais das vitaminas e minerais. Essas alterações proporcionam um impacto econômico significativo em relação à nutrição animal. Nesse sentido, objetivou-se com esta revisão trazer informações acerca de vitaminas e minerais na nutrição de bovinos em pastejo. -/- Palavras-chave: Alimentação animal; forragem; pastagem; requerimentos nutricionais; ruminantes; vitaminas lipossolúveis (Source: AGROVOC). -/- ABSTRACT Animal feed is the factor that most burdens a production system. Thus, the use of different animal feeding strategies is still the great challenge of animal nutrition, taking into account the nutritional requirements of different categories of ruminants, especially cattle in tropical regions, given that seasonality in forage production directly affects cattle production, promoting inadequacy in meeting the nutritional requirements of animals, mainly in minerals and vitamins. A diet that does not meet the nutritional requirements of ruminants generates losses in the production system, in addition to, in more serious cases, causing the loss of the animal. Studies that address the effect and importance of vitamins and minerals in bovine nutrition are scarce and necessary. Recently the National Research Council (NRC) presented new records of the nutritional requirements of vitamins and minerals. These changes provide a significant economic impact on animal nutrition. In this sense, the objective of this review was to bring information about vitamins and minerals in the nutrition of grazing cattle. -/- Keywords: Animal feeding; fat soluble vitamins; forage; nutritional requirements; pasture feeding; ruminants (Source: AGROVOC). -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- 1. Cavalcanti CPL, Silva e Macedo TJ, Gois GC, Menezes VG, Monte APO, Silva AD, Silva DJM, Silva EO, Araújo GGL, Rodrigues RTS, Wischral A, Matos MHT, Queiroz MAA. 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Commensal and pathogenic organisms employ camouflage and mimicry to mediate mutualistic interactions and predator escape. However, the immune mechanisms accounting for the establishment and maintenance of symbiotic bacterial populations are poorly understood. A promising hypothesis suggests that molecular mimicry, a condition in which different organisms share common antigens, is a mechanism of establishing tolerance between commensals and their hosts. On this view, certain bacteria may mimic the structural features of some of their host’s T-cell receptors (TCRs), namely those that survive (...) thymic selection due to their lack of complementarity to self-antigens. With such “holoimmunity” the mimicking micro-organisms avoid immune recognition as the copied TCRs become mirror images of an extended super-organismal self, consisting of symbiotic and host antigens. Accordingly, analysis of genomic and metagenomic data suggests a tripartite mimicry between TCRs, self-antigens, and commensal antigens that would serve as the basis for immune tolerance between these populations. And conversely, in an autoimmune scenario, both symbiotic microbes and the mimicked host tissue would be targeted for immune destruction. (shrink)

“Indeed, we now know that the proportion of genetic sequences on earth that belongs to visible organisms is negligible. Furthermore, only 15% of the genetic sequences found in the samples from the environment and from feces analyzed in metagenomic studies belong to the three domains of microbes currently recognized in the tree-of-life framework – bacteria, archaea, and eukaryotes. Viruses contain another 15-30% of these genetic sequences.” This means that the majority of unidentified genetic sequences pose an unresolved problem. Where do (...) they come from? New genes suddenly appear, called ORFans (“orphan genes”) without any precursors. They may be produced by gene duplication, or fusion, or some other unknown process. Yet, Darwin’s tree of life concept would make it impossible to consider such processes. The transfer of genetic sequences from parasites to hosts could involve hundreds of genes for bacteria or viruses. But, as Raoult writes, “the current classification of the domains of life is based on the ribosome – the production apparatus of proteins – which does not exist in these viruses.” Adherence to the dogmatism of Darwin thus prevents these new discoveries, that overturn his century-and-a-half old teachings, from ever reaching the new generation of scientists. Raoult concludes, "Genetic research, in particular, must be free to find new models to explain, and enhance, twenty-first-century scientific discovery. Today, Darwin’s theory of evolution is more a hindrance than a help, because it has become a quasi-theological creed that is preventing the benefits of improved research from being fully realized.". (shrink)