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    <article-meta>
      <title-group>
        <article-title>uc_Milk: An ontology for scientifically-based unambiguous characterization of mammalian milks, their composition and the biological processes giving rise to their creation</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Emeline Colet</string-name>
          <email>emeline.colet@etu.chimie-paristech.fr</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Matthew Lange</string-name>
          <email>mclange@ucdavis.edu</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Department of Food Science and Technology University of California Davis Davis</institution>
          ,
          <addr-line>CA</addr-line>
          ,
          <country country="US">USA</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Ecole Nationale Supérieure de Chimie de Paris Chimie ParisTech Paris</institution>
          ,
          <country country="FR">FRANCE</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>- Recent efforts in biological ontology go to great lengths to unambiguously categorize biological entities and phenomena of the natural world, as well as their relationships with each other. This paper illustrates the importance of unambiguously characterizing mammalian milk because milk is a complex mixture of many chemical components and thus represents a key role in infant nourishment and development. In addition to the build of a computable knowledge base around mammalian milk, ontological modeling of this aspect of biology and chemistry enable increased understanding of mammalian milk composition and the biological structures and biochemical processes giving rise to their creation. Utilizing unambiguous vocabularies to compare human milk with other mammalian milks relative to the biological and behavioral survival challenges facing varied mammalian organisms and the phenotypic qualities each milk confers, is a fundamental goal of this project.</p>
      </abstract>
      <kwd-group>
        <kwd>- mammalian modeling</kwd>
        <kwd>biological processes</kwd>
      </kwd-group>
    </article-meta>
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      <title>-</title>
      <p>
        One foundational design pattern for creating uc_Milk is an
ontology for unambiguous characterization of mammalian milks,
their composition and the biological processes giving rise to their
creation. Available online at the GitHub website
github.com/ICFOODS/uc_Milk, uc_Milk is part of a larger multi-ontology
framework [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ] currently being housed within the International
Center for Food Ontology Operability, Data, and Semantics.
ICFOODS at UC Davis [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. Milk is at once, a consumable
beverage, an ingredient at the heart of the dairy industry, and
often the sole nutritive source for infants--being both a source of
dietary metabolites as well as a transport mechanism for
xenobiotic agents. In all of its roles as a food/ingredient source,
milks are known to confer specific health phenotypes as they
interact with specific genotypes. Yet to date milk has received
very limited attention in the world of ontological research.
We used the Basic Formal Ontology as an upper ontology
because of its ubiquity in biological and biomedical ontologies,
for facilitating integration by way of meta-concepts. In addition
to characterizing the biological and biochemical structures and
processes related to mammalian milks, since milk is a
commodity as well as an essential biological fluid, uc_Milk
ontology considers social, commercial, and environmental
      </p>
      <p>Lactation is the hallmark underlying biological force driving
the mother-infant dyad in Mammalia. The significant energetic
and metabolic costs of lactation imposed to the mother suggests
that milk’s role in infant health extend well beyond simple
nutrition. Millennia of selective pressures on the mother-infant
dyad, have conferred in milk a dual purpose: an optimal source
of nutrients, and a delivery vehicle for bioactive agents. Milk is
known as nature’s most complete food because of its complex
mixture of bioactive components and essential nutrients such as
protein, fat, carbohydrate, minerals, vitamins, and
physiologically active substances. Aside from nutritional values
of milk, biologically active compounds such as casein and whey
proteins have been found to be increasingly important for
physiological and biochemical functions that have crucial
impacts on human metabolism and health. Accordingly, the
infant gut and its associated microbiota are adapted not only for
the utilization and absorption of milk macronutrients, but also to
respond to non-nutritive, yet bioactive molecular entities.
Important non-nutritive, bioactive agents in human milk include
an astonishing high number of complex oligosaccharides, and a
plethora of glycoconjugated proteins and lipids. Complex
prebiotic oligosaccharides are known to be present in domestic
animal milks, yet are in low abundance relative to human milk, a
known source of prebiotic oligosaccharides with important
effects on human health. Characterization of these molecules,
known as Human Milk Oligosaccharides or HMOs started in the
1960s, yet even today, their analysis remains a challenging task
due to the large number of structures and their structural
complexity. No commercially viable processes for
manufacturing these complex and important milk bioactives
exist, making the third largest component of breast milk,
conspicuously absent in today’s infant formulas, weaning foods,
medical foods and everyday dairy products. Understanding the
extent and types of oligosaccharides present in bovine milk is an
important step towards determining the feasibility of developing
commercial sources. The identification, annotation and
characterization of oligosaccharides and other bioactive
compounds in milk in is a necessary step to evaluate the
processes giving rise to their formation, and will enable future
scale-up processes for recovering these ingredients for
commercial applications.</p>
      <p>
        The tremendous variation of milk compositions that occurs
among mammalians is one of the particularly interesting aspects
of lactation biology. As mammals include the largest animals of
the planet, a classification has been established: mammalians
have been separated into two major groups, placental and
nonplacental mammals. Classification systems based on molecular
studies reveal three major groups or lineages of placental
mammals: Afrotheria, Xenarthra and Boreoeutheria which have
been divided in clades, superorders and orders [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. The aim
is to compare composition of a great number mammalian milk
with human milk based on fat, protein, sugar, vitamin, dry matter
and energy content and to understand the influence of various
factors such as consumed diet, lactation time, habitat and many
others on milk composition [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. Another important part of
developing this ontology is to describe the processes giving rise
to milk creation. Indeed milk is a complex mixture whose
composition reflects the activities of distinct secretion and
transport processes of the mammary gland and mirrors the
differing nutritional requirements of mammalian mammary
gland neonates [6]. To accomplish those main goals, uc_Milk
covers two main points of view: on the one hand because milk is
a complex biologically derived fluid, uc_Milk will serve basic
science but on the other hand, since milk is involved in many
dairy products, this ontology is also designed to facilitate
utilization in commercial and industrial foods.
      </p>
      <p>The first part of uc_Milk has breastmilk as starting point: as
mammary glandular fluid, milk supplies water and chemicals
components to the neonate for his survival, proper development,
and vigorous growth (Figure 1). uc_Milk provides structures in
three stages of life cycle: infant stage with breastfeeding thanks
to milk, pregnancy stage with biological modifications and
hormones, and lactation stage which is divided in four steps :
mammogenesis, lactogenesis, galactopoiesis and involution. At
the same time, lactogenesis is classified as subclass of biological
process due to the secretory differentiation of mammary gland
and the biological production of milk. Additionally, lactation
system described as subclass of exocrine system includes the
biological functional anatomy of the lactating mammary gland
and the biological transport and secretion pathways because
solutes can enter milk through both transcellular and paracellular
routes. Transcellular routes are divided in four general pathways,
two for the secretion of endogenous substances and two other for
the transport of exogenous substances (Figure 2) [6]. The
biological factors of milk production overlap with the
breastfeeding behavior of uc_Eating ontology.</p>
      <p>The second part of uc_Milk is industrial and food focused.
uc_Milk provides structures in milk processing, milk process,
milk producing, milk production as well as food products : milk
is involved in many dairy food products such as butter, cream, or
cheese. Milk attributes are subclasses of food product and the
milk sensory quality attribute overlap with the uc_Sense
ontology. The format of the ontology connects the subclasses of
milk processing process and milk production process to the
uc_Processing ontology. Furthermore, uc_Milk characterizes the
composition of different mammalian milk as subclass of milk
producing entity.</p>
      <p>Using Protégé, with the streamlined interface and the
program's ability to add changes and import existing ontology
files improved the flow of classification and improved the
reproducibility of uc_Milk. This ontology is still at an early stage
so we are just beginning the process of adding axioms and we
have not yet tested this initial ontology. Sustainability plans for
the ontology will be developed once we receive initial feedback
from the community about how paths forward for integration
with related ontologies. Entity identifiers will be established after
feedback is received from ICBO participants, and integration
partners are identified.</p>
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