Flow chart of the population study.

<p>Flow chart of the population study.</p

Criteria indicating HT according to HT subgroups.

<p>OHT: optimal hypothermia treatment, LHT: late hypothermia treatment, NIHT: non indicated hypothermia treatment, *** p<10⁻³, **10⁻³≤p<10⁻², *10⁻²≤p<0.05,</p><p>ns : not significant.</p

Organization of care and birth circumstances according to HT subgroups.

<p>OHT: optimal hypothermia treatment, LHT: late hypothermia treatment, NIHT: non indicated hypothermia treatment, *** p<10⁻³, **10⁻³≤p<10⁻², *10⁻²≤p<0.05,</p><p>ns : not significant,</p

General characteristics of the whole study population.

<p>: Switch off incubator or ice packs.</p

Characteristics of HT, adverse events, complications and short-term outcomes according to the different HT subgroups.

<p>OHT: optimal hypothermia treatment, LHT: late hypothermia treatment, NIHT: non indicated hypothermia treatment, +Switch off incubator or ice packs, *** p<10⁻³,</p><p>10⁻³≤p<10⁻², *10⁻²≤p<0.05, ns : not significant.</p

Interest of heterogeneous methods in pathway completion and filling thanks to tracking of process metadata.

<p>Completion of the 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I and the tetrahydrofolate biosynthesis pathways in <i>E</i>. <i>siliculosus</i> via the combination of annotation (yellow), orthology (green) and gap-filling (blue). The dihydrofolate compound with the dotted line is an instance of the dihydrofolate-glu-n class, following MetaCyc classes ontology structure. The class compound is the original reactant of the dihydrofolatereduct-rxn reaction retrieved with annotation, whereas the previous reaction of the pathway (dihydrofolatesynth-rxn) produces the instance dihydrofolate. Hence the gap-filling step that, using an extended version of MetaCyc, selects an instantiated version of dihydrofolatesynth-rxn that consumes the instance dihydrofolate.</p

AuReMe workspace.

<p><i>Overview of the AuReMe workspace</i>. Admissible inputs include standard formats in genomics and metabolic model fields that can be outputs of major reconstruction platforms. <i>AuReMe</i> acts as a workflow controller to administer the reconstruction or modification of the GSM performed by heterogeneous and independent tools. The latter are part of the services of <i>AuReMe</i> (reconstruction tools, analyses, manual curation) and can be chained together, either in a pre-set pipeline or in a customized one. In any case the <i>PADMet</i> data manager stores adequate information regarding the model and its metadata, most importantly the process ones, that keeps track of the modifications performed (at what step a reaction was added, by which tool etc.). At any time, the reconstruction can be monitored locally via an automatically-generated wiki that informs the user about the state of the model. Outputs of <i>AuReMe</i> can be self-sufficient or be integrated again in many existing platforms.</p

<i>Tisochrysis lutea</i> metabolic model exploration: Origin of reactions according to the reconstruction pipeline.

<p>(A) Comparison of the numbers of EC numbers introduced in the network either by the annotation pipeline or by the orthology-based analysis 898 enzymes were identified via annotation-based information and 790 enzymes through orthology-based data, among which 524 were already identified via annotation information. (B) <i>Number of T-Iso ortholog enzymes according to their origin in template models</i>. For each of the 790 T-Iso ortholog enzymes, the figure depicts in which of the four template models an ortholog of the enzyme had been identified. The four templates used were: <i>A</i>. <i>thaliana</i>, <i>C</i>. <i>reinhardtii</i>, <i>E</i>. <i>siliculosus</i> and <i>Synechocystis</i> sp. PCC 6803 to decipher ortholog enzymes in <i>T</i>. <i>lutea</i>. (C) <i>T-Iso carnosine biosynthesis</i>. Reconstruction of T-Iso carnosine synthesis pathway was performed using three sources of data (i) T-Iso genome annotations (cyan star); (ii) template metabolic models (stars) of four organisms: <i>A</i>. <i>thaliana</i> (blue), <i>C</i>. <i>reinhardtii</i> (green), <i>E</i>. <i>siliculosus</i> (red), and <i>Synechocystis</i> sp. (yellow) with orthology-based information; (iii) complete proteomes of the four organisms (squares) with sequence alignment information (best reciprocal hit in blasts). All reactions of the T-Iso carnosine biosynthesis are common to the four organisms except for three of them: ASPDECARBOX-RXN, HISTIDPHOS-RXN, and CARNOSINE-SYNTHASE-RXN. The first seems to belong to an alternative pathway to produce β-alanine, also found in <i>C</i>. <i>reinhardtii</i>, <i>Synechocystis</i> sp and <i>Candidatus Phaeomarinobacter ectocarpi</i>, a symbiotic bacterium to <i>E</i>. <i>siliculosus</i>. HISTIDPHOS-RXN was not found in <i>E</i>. <i>siliculosus</i> but was identified in its symbiotic bacterium <i>Candidatus</i> Phaeomarinobacter ectocarpi. CARNOSINE-SYNTHASE-RXN was only identified in algae (<i>C</i>. <i>reinhardtii</i>, <i>E</i>. <i>siliculosus</i> and <i>T</i>. <i>lutea</i>).</p

Screen captures of several pages of the local wiki and the interactions between them.

<p>A local wiki-based export of the GSM facilitates user-interface exploration and traceability of the reconstruction procedure. Several screenshots of a wiki are displayed, arrows represent the link between pages. Notably, reactions can be sorted and explored according to reconstruction categories, tools and sources. The navigation panel enables exploring and comparing the contributions of each tool used in the “à la carte” GSM reconstruction pipeline. Pathways can be sorted based on their completion rate.</p

Survey of 19 GSM reconstruction procedures.

<p>Variability of reference ID-databases, available annotations and metadata about reactions and heterogeneity of the methods used in each GSM reconstruction pipeline.</p