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<body xmlns="http://www.w3.org/1999/xhtml">We present a novel methodology to construct a Boolean dynamic model from time series metagenomic information and integrate this modeling with genome-scale metabolic network reconstructions to identify metabolic underpinnings for microbial interactions. We apply this in the context of a critical health issue: clindamycin antibiotic treatment and opportunistic Clostridium difficile infection. Our model recapitulates known dynamics of clindamycin antibiotic treatment and C. difficile infection and predicts therapeutic probiotic interventions to suppress C. difficile infection. Genome-scale metabolic network reconstructions reveal metabolic differences between community members and are used to explore the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of our computational model, that B. intestinihominis can in fact slow C. difficile growth.</body>
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<p>Genus: Coprobacillus</p><p>Family: Erysipelotrichaceae</p></body>
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<p>Family: Enterobacteriaceae</p><p>Order: Enterobacterales</p><p>Klebsiella species and Escherichia coli (E. coli) are part of the Enterobacteriaceae family and are commonly found in the gut microbiome.</p></body>
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<p>Genus: Enterococcus</p><p>Family: Enterococcaceae</p><p>Opportunistic Pathogen</p></body>
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<p>Genus: Blautia</p><p>Family: Lachnospiraceae</p><p>Blautia are common gut bacteria and aid in the digestion of complex carbohydrates.</p></body>
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<p>Refers to microorganisms that are not in the ten most abundant genera in the gut microbiome.</p></body>
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<p>Family: Lachnospiraceae</p><p>Order: Clostridiales</p><p>Lachnospiraceae is an common member of the human gut microbiota that degrades complex polysaccharides to short-chain fatty acids.</p></body>
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<p>Class: Mollicutes</p><p>Phylum: Tenericutes</p><p>Experiment data on mice gut bacteria indicates that Mollicutes is an abundant member of the gut microbiome.</p></body>
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<p>Genus: Akkermansia</p><p>Family: Akkermansiaceae</p><p>Gram-negative bacteria</p><p>Akkermansia is one of the most abundant members of the human gut microbiota.</p></body>
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<p>Genus : Barnesiella</p><p>Family: Porphyromonadaceae</p><p>Gram-negative bacteria</p><p>Barnesiella is usually only found at relatively ow levels in the gut.</p></body>
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<p>Genus: Clostridium</p><p>Family: Clostridiaceae</p><p>Spore-forming, gram-positive bacillus</p><p>Opportunistic pathogen</p></body>
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<p>An antibiotic that is known to be effective against some gram-positive and anaerobic bacteria. The summarized mechanism of action is that it is effective by blocking peptide formation via direct binding to sites on ribosomes, which inhibits cell growth.</p></body>
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<p>Family: Lachnospiraceae</p><p>Order: Clostridiales</p><p>Lachnospiraceae is an common member of the human gut microbiota that degrades complex polysaccharides to short-chain fatty acids.</p></body>
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<p>Blautia, Clostridium_difficile, Enterobacteriaceae, and Mollicutes are positive regulators of Enterococcus. Coprobacillus is a non-dominant inhibitor of Enterococcus.</p></body>
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<qual:transition qual:id="tr_S_3">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Blautia activates itself when Coprobacillus is inactive. Coprobacillus activates Blautia when Blautia is inactive. Enterococcus also activates Blautia.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_3_in_S_3" qual:qualitativeSpecies="S_3" qual:sign="dual" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Blautia regulates its own activity.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_3_in_S_10" qual:qualitativeSpecies="S_10" qual:sign="dual" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Coprobacillus regulates Blautia.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_3_in_S_2" qual:qualitativeSpecies="S_2" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Enterococcus positively regulates Blautia.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_3" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<or/>
<apply>
<or/>
<apply>
<or/>
<apply>
<eq/>
<ci> S_2 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<eq/>
<ci> S_3 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_10 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_3 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_3 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_10 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_4">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Other, Lachnospiraceae_other, and Lachnospiraceae are activators of Other. Clindamycin is a negative regulator of Other which expresses dominance over Other, Lachnospiraceae_other, and Lachnospiraceae.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_4_in_S_5" qual:qualitativeSpecies="S_5" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae positively regulates Other.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_4_in_S_4" qual:qualitativeSpecies="S_4" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Other activates itself.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_4_in_S_11" qual:qualitativeSpecies="S_11" qual:sign="negative" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Clindamycin negatively regulates Other.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_4_in_S_12" qual:qualitativeSpecies="S_12" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae_other positively regulates Other.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_4" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<or/>
<apply>
<or/>
<apply>
<and/>
<apply>
<eq/>
<ci> S_5 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_4 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_12 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_5">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Other, Lachnospiraceae_other, and Lachnospiraceae activate Lachnospiraceae. Clindamycin is a negative regulator of Lachnospiraceae which expresses dominance over Other, Lachnospiraceae_other, and Lachnospiraceae.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_5_in_S_5" qual:qualitativeSpecies="S_5" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae positively regulates itself.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_5_in_S_4" qual:qualitativeSpecies="S_4" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Other positively regulates Lachnospiraceae.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_5_in_S_11" qual:qualitativeSpecies="S_11" qual:sign="negative" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Lachnosporaceae populations drop drastically after antibiotic treatment, including treatment with Clindamycin.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_5_in_S_12" qual:qualitativeSpecies="S_12" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae_other positively regulates Lachnospiraceae.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_5" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<or/>
<apply>
<or/>
<apply>
<and/>
<apply>
<eq/>
<ci> S_4 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_5 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_12 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_6">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Mollicutes activates itself.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_6_in_S_6" qual:qualitativeSpecies="S_6" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Mollicutes activates itself.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_6" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> S_6 </ci>
<cn type="integer"> 1 </cn>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_7">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Akkermansia is activated by Coprobacillus.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_7_in_S_10" qual:qualitativeSpecies="S_10" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Coprobacillus is inferred to positively regulate Akkermansia through an unknown mechanism.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_7" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> S_10 </ci>
<cn type="integer"> 1 </cn>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_8">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Other, Lachnospiraceae_other, and Lachnospiraceae activate Barnesiella. Clindamycin is a negative regulator of Barnesiella which expresses dominance over Lachnospiraceae, Lachnospiraceae_other, and Other.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_8_in_S_5" qual:qualitativeSpecies="S_5" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae positively regulates Barnesiella through an unknown mechanism.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_8_in_S_4" qual:qualitativeSpecies="S_4" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Other positively regulates Barnesiella through an unknown mechanism.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_8_in_S_11" qual:qualitativeSpecies="S_11" qual:sign="negative" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>A day after a single dose of Clindamycin resulted in a significant loss of Barnesiella populations.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_8_in_S_12" qual:qualitativeSpecies="S_12" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae_other positively regulates Barnesiella.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_8" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<or/>
<apply>
<or/>
<apply>
<and/>
<apply>
<eq/>
<ci> S_5 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_12 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_4 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_9">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Clostridium_difficile activates itself. Barnesiella is a negative regulator of Clostricium_difficile which also expresses dominance over it.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_9_in_S_9" qual:qualitativeSpecies="S_9" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Clostridium_difficile activates itself.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_9_in_S_8" qual:qualitativeSpecies="S_8" qual:sign="negative" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Clostridium_difficile grows slower when co-cultured with B. intestinihominis. The mechanism behind this decreased growth when when exposed to B. intestinihominis is unknown, but indicates that Barnesiella negatively regulates Clostridium_difficile proliferation.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_9" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<and/>
<apply>
<eq/>
<ci> S_9 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_8 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_11">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Clindamycin activates itself.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_11_in_S_11" qual:qualitativeSpecies="S_11" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Clindamycin activates itself.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_11" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
<qual:transition qual:id="tr_S_12">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Other, Lachnospiraceae_other, and Lachnospiraceae are activators of Lachnospiraceae_other. Clindamycin is a negative regulator of Lachnospiraceae_other which expresses dominance over Other, Lachnospiraceae_other, and Lachnospiraceae.</p></body>
</notes>
<qual:listOfInputs>
<qual:input qual:id="tr_S_12_in_S_5" qual:qualitativeSpecies="S_5" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae positively regulates Lachnospiraceae_other.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_12_in_S_4" qual:qualitativeSpecies="S_4" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Other positively regulates Lachnospiraceae_other.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_12_in_S_11" qual:qualitativeSpecies="S_11" qual:sign="negative" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Lachnosporaceae populations drop drastically after antibiotic treatment, including treatment with Clindamycin.</p></body>
</notes>
</qual:input>
<qual:input qual:id="tr_S_12_in_S_12" qual:qualitativeSpecies="S_12" qual:sign="positive" qual:thresholdLevel="1" qual:transitionEffect="none">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Best-fit extension was used to determine that Lachnospiraceae_other positively regulates itself.</p></body>
</notes>
</qual:input>
</qual:listOfInputs>
<qual:listOfOutputs>
<qual:output qual:qualitativeSpecies="S_12" qual:transitionEffect="assignmentLevel"/>
</qual:listOfOutputs>
<qual:listOfFunctionTerms>
<qual:defaultTerm qual:resultLevel="0">
</qual:defaultTerm>
<qual:functionTerm qual:resultLevel="1">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<or/>
<apply>
<or/>
<apply>
<and/>
<apply>
<eq/>
<ci> S_5 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_4 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<eq/>
<ci> S_12 </ci>
<cn type="integer"> 1 </cn>
</apply>
<apply>
<not/>
<apply>
<eq/>
<ci> S_11 </ci>
<cn type="integer"> 1 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</qual:functionTerm>
</qual:listOfFunctionTerms>
</qual:transition>
</qual:listOfTransitions>
<listOfCompartments>
<compartment constant="true" id="extracellular" name="extracellular"/>
<compartment constant="true" id="cytosol" name="cytosol"/>
</listOfCompartments>
</model>
</sbml>