You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


---
bibliography:
- 'Ref.bib'
title: Relation between Gene Content and Taxonomy in Chloroplasts
---

**Abstract** The aim of this study is to investigate the relation that can be found between the phylogeny of a large set of complete chloroplast genomes, and the evolution of gene content inside these sequences. Core and pan genomes have been computed on *de novo* annotation of these 845 genomes, the former being used for producing well-supported phylogenetic tree while the latter provides information regarding the evolution of gene contents over time. It details too the specificity of some branches of the tree, when specificity is obtained on accessory genes. After having detailed the material and methods, we emphasize some remarkable relation between well-known events of the chloroplast history, like endosymbiosis, and the evolution of gene contents over the phylogenetic tree.

Chloroplasts, Phylogeny, Taxonomy, Core and Pan genomes, Gene content

Introduction
============

Understanding the evolution of DNA molecules is a very complex problem, and no concrete and well established solution exists at present regarding the case of large DNA sequences. Our objective in this article is to start to show that this complex problem can be (at least partially) solved when considering genomes of reasonable size and who faced a rational number of recombination, like in the chloroplasts case. However, various difficulties remain to circumvent when dealing with such a specific case, and solving them require the design of new ad hoc tools. Candidates for such tools are presented in this article, and are applied on the chloroplast case.

Chloroplasts are one of the numerous types of organelles in the plant cell. The term of chloroplast comes from the combination of chloro and plastid, meaning that it is an organelle found in plant cells that contains the chlorophyll. Chloroplast has the ability to convert water, light energy, and carbon dioxide ($CO_2$) into chemical energy by using carbon-fixation cycle [@uzman2003molecular] (also called *Calven Cycle*, the whole process being called photosynthesis). This pivotal role explains why chloroplasts are at the basis of most trophic chains and are thus responsible for evolution and speciation.

Consequently, investigating the evolutionary history of chloroplasts is of great interest, and our long-term objective is to explore it by the mean of ancestral genomes reconstruction. This reconstruction will be achieved in order to discover how the molecules have evolved over time, at which rate, and to determine whether this way can present evidence of their cyanobacteria origin. This long-term objective necessitates numerous intermediate research advances. Among other things, it supposes to be able to apply the ancestral reconstruction on a well-supported phylogenetic tree of a representative collection of chloroplastic genomes. Indeed, sister relationship of two species must be clearly established before trying to reconstruct their ancestor. Additionally, it implies to be able to detect content evolution (modification of genomes like gene loss and gain) along this accurate tree. In other words, *gene content evolution* on the one hand, and *accurate phylogenetic inference* on the contrary, must be carefully regarded *in the particular case of chloroplast sequences*, as the two most important prerequisites in our quest of the last universal common ancestor of these chloroplasts.

  --------------- --------- ------------ -------- ---------- -----------
  Taxonomy         nb. of    min length    max     average    standart
                   genomes     length     length              deviation
  Alveolata           4        85535      140426   115714.2    19648.3
  Cryptophyta         2        121524     135854   128689.0    7165.0
  Euglenozoa          7        80147      143171   98548.7     19784.5
  Haptophyceae        3        95281      107461   102683.6    5307.6
  Rhodophyta          9        149987     217694   183755.5    18092.2
  Stramenopiles      35        89599      165809   124895.1    15138.0
  Viridiplantae      775       80211      289394   150194.9    20376.8
  --------------- --------- ------------ -------- ---------- -----------

  : Information on chloroplast sizes at highest taxonomic level[]{data-label="tab:genome size"}

The objective of this research work is to make significant progress in this quest, by providing material and methods required in the study of chloroplastic sequence evolution. Contributions of this article consist in the computation of core and pan genomes of the 845 complete genomes available on the NCBI, in the production of a well-supported phylogenetic tree based on core sequences as large as possible, and on the study of the produced data. In particular, we start to emphasize some links between the phylogenetic tree and evolution of gene content.

The paper is structured as follows. In the next section, material and methods applied in this study are presented, which encompass genome acquisition and annotation, core and pan genome analysis, and phylogenetic investigations. Obtained results related to such analyzes are detailed in Section \[sec:obtainedRes\], on the chloroplast case. This article ends with a conclusion section, in which the study is summarized and intended future work is outlined.

Materials and methods {#Data acquisition}
=====================

Data acquisition
----------------

A set of 845 chloroplastic genomes (green algae, red algae, gymnosperms, and so on) has been downloaded from the NCBI website, representing all the available complete genomes at the date of March, 2016 (see Table \[tab:genome size\]). An example of such sequences, taken from the *Streptophyta* clade (a *Viridiplantae*), is provided in Table \[tab:Streptophyta\]. Note that this set does not really constitute a very balanced representation of the diversity of plants, as plants of particular and immediate interest to us like *Viridiplantae* are first sequenced. We must however deal with such bias, as genomic data acquisition is most of the time human-centred. This set of sequences presents too a certain variability in terms of length, as detailed in Table \[tab:genome size\].

  ---------------------------- -------------- ---------- -------
  Organism name                  Accession     Sequence   Nb of
                                   number       length     CDS
  *Epimedium sagittatum*        NC\_029428.1    158273     85
  *Berberis bealei*             NC\_022457.1    164792     267
  *Torreya fargesii*            NC\_029398.1    137075     100
  *Lepidozamia peroffskyana*    NC\_027513.1    165939     93
  *Actinidia chinensis*         NC\_026690.1    156346     271
  *Quercus aliena*              NC\_026790.1    160921     259
  *Quercus aquifolioides*       NC\_026913.1    160415     176
  *Sedum sarmentosum*           NC\_023085.1    150448     99
  ---------------------------- -------------- ---------- -------

  : Example of genomes information of *Streptophyta* clade

\[tab:Streptophyta\]

Each genome has been annotated with DOGMA [@RDogma], an online automatic and accurate annotation tool of organellar genomes, following a same approach than in [@Alkindy2014]. To apply it on our large scale, we have written (with the agreement of DOGMA authors) a script that automatic send requests to the website. By doing such annotations, the same gene prediction and naming process has been applied with the same average quality of annotation. In particular, when a gene appears twice in the considered set of genomes, it receives twice the same name (no spelling error). At this level, each genome is then described by an ordered list of gene names, with possible duplications (other approaches for the annotation stage are possible, see, *e.g.*, [@Alkindy2014]). This description will allow us to investigate, later in this article, the evolution of gene content among the species tree, leading to the study of core and pan genomes recalled below.

Core and pan genome {#Core and pan genome}
-------------------

Given a collection of genomes, it is possible to define their core genes as the common genes that are shared among all the species, while the pan genome is the union of all the genes that are in at least one genome (*all* the species have each core gene, while a pan gene is in *at least one* genome). Shared genes are evidences of evolution from a common ancestor and of the relatedness of chloroplast organisms.

  ----------------- --------- -------------- -------------- --------------
     *Taxonomy*        Nb.       Min N.b        Max N.b      Average Nb.
                     genomes   of pan genes   of pan genes   of pan genes
     *Alveolata*        4          253            266           262.25
    *Cryptophyta*       2          258            259           258.5
    *Euglenozoa*        7          193            267          253.428
   *Haptophyceae*       3          251            266          258.333
    *Rhodophyta*        9          156            267          246.222
   *Stramenopiles*     35           73            271          238.971
   *Viridiplantae*     775          85            271          229.827
  ----------------- --------- -------------- -------------- --------------

  : Summarized properties of the pan genomes at the highest taxonomic level.[]{data-label="taxo1"}

To distinguish and determine the core genes may be of importance either to identify the specificity and the shared functionality of a given set of species, or to evaluate their phylogeny using the largest set of shared coding sequences. In the case of chloroplasts, an important category of genome modification is indeed the loss of functional genes, either because they become ineffective or due to transfer to the nucleus. Thereby, a small number of gene loss among species may indicate that these species are close to each other and belong to a similar lineage, while a significant loss means distant lineages.

So core genome is obviously of importance when inferring the phylogenetic relationship, while accessory genes of pan genome explain in some extend each species specificity. We have formerly proposed three approaches for eliciting core genomes. The first one uses correlations computed on predicted coding sequences [@Alkindy2014], while the second one uses all the information provided during an accurate annotation stage [@Alkindy_BIBM2014]. The third method takes the advantages from the first two approaches, by considering gene information and DNA sequences, in order to find the targeted core genome [@Alkindy_IWWBIO].

![Phylogenetic tree overview\[fig:final\]](tree111.jpg){width="50.00000%"}

We have found the core genome[^1] of each selected family by using the second method described in the previous paragraph [@Alkindy_BIBM2014]. Obtained results regarding gene content are discussed in the next section. The core genome has been used too for our phylogenetic investigation of chloroplast sequences, which has been applied as described hereafter.

Phylogeny study
---------------

The next step when trying to reconstruct the evolution of gene content over time is to deeply investigate the phylogeny of these chloroplasts, in order to obtain a tree as supported as possible. Indeed, a branching error in the tree may lead to an erroneous transmission of an ancestral state, which is dramatically perpetuated until reaching the last universal common ancestor. However, as we considered all existing plant taxa, we faced chloroplastic sequences that have diverged a lot since two billion of years, so the core genome of these 845 sequences is very small when compared with sequence length of each representative, and inferring a tree on such a partial information will probably lead to numerous errors.

The approach that has been regarded in our study was then to group the plant families per close packets (same family in the taxonomy). Such grouping has enlarged the number of shared gene sequences (core genes of the considered family) on which a more representative phylogeny can be computed [@DBLP:journals/corr/AlKindyGCSPB15]. After having aligned the core genes of each family using MUSCLE [@edgar2004muscle] on our supercomputer facilities, we then have inferred a phylogenetic tree per family.

![The distributions of chloroplast genomes depending on the genomes size.\[fig:genes\]](ThesizeofGenomes3.png){width="50.00000%"}

To obtain such a tree, the RAxML [@stamatakis2014raxml; @rizzo2007review] program has been employed to compute the phylogenetic maximum-likelihood (ML) function with the setup described hereafter. General Time Reversible model of nucleotide substitution, with $\Gamma$ model of rate heterogeneity and hill-climbing optimization method. The *Prochlorococcus marinus* (NC\_009091.1) cyanobacteria species has finally been chosen as outgroup, due to the supposed cyanobacteria origin of chloroplasts.

After such a computing, if all bootstrap values are larger than 95%, then we have consider that the phylogeny is resolved, as the largest possible number of genes has led to a very well supported tree. In case where some branches are not supported, we can wonder whether a few genes can be incriminated in this lack of assistance, for a large variety of reasons encompassing homoplasy, stochastic errors, undetected paralogy, incomplete lineage sorting, horizontal gene transfers, or even hybridization. Such problem has been resolved by finding the largest subset of core genes leading to the most supported tree, by the heuristic approach coupled with statistical LASSO tests described in [@alsrraj2015well; @DBLP:journals/corr/AlKindyGCSPB15]. Obtained trees are then merged on a well-supported and representative supertree.

Obtained results {#sec:obtainedRes}
================

Phylogenetic investigations
---------------------------

The approach detailed in the previous section has led to a well supported phylogenetic tree of the whole available chloroplasts, with the ordered list of genes at each leaf of the tree. An overview of the latter is provided in Figure \[fig:final\]. Obtained tree available too on our website is in general coherent with the NCBI taxonomy, except in some specific locations.

By going into the details of the obtained tree, it is well known that the first plants endosymbiosis ended in a great diversification of lineages comprising Red Algae, Green Algae, and Land Plants (terrestrial). The interesting point in the production of our results is that the organisms resulting from the first endosymbiosis are distributed in each of the lineages found in the chloroplast genome structure evolution as outlined in Figure \[fig:final\].

More precisely, all Red Algae chloroplasts are grouped together in one lineage, while Green Algae and Land Plant chloroplasts are all in a second lineage. Furthermore, organisms resulting from the secondary endosymbioses, as listed in Table \[taxo2\], are well localized in the tree: both the chloroplasts of Brown Algae and *Dinoflagellates* representatives are found exclusively in the lineage also comprising the Red Algae chloroplasts from which they evolved, while the *Euglens* is related to Green Algae from which they evolved. This latter makes sense regarding biology, history of lineages, and theories of chloroplasts origins (and so photosynthetic ability) in different *Eucaryotic* lineages [@li2013complete].

Gene content
------------

Let us now investigate the gene content level of the tree. Indeed, genes are rearranged in the genome by evolutionary events like insertion, deletion, transposition, and inversion, which are called genome rearrangements [@suyama2001evolution]. Such rearrangements can be studied, considering that we have both the gene contents and the phylogeny. A general overview of obtained results, in terms of gene contents (pan genome) evolution at the top taxonomy level, is provided in Table \[taxo1\], and it is detailed for the following taxonomic level in Table \[taxo2\].

The core genome is constituted by 36 coding sequences, namely: *ATPA, ATPB, ATPH, ATPI, PETB, PETG, PSAA, PSAB, PSAC, PSAJ, PSBA, PSBC, PSBD, PSBE, PSBF, PSBH, PSBI, PSBJ, PSBL, PSBN, PSBT, PSI\_PSBT, RBCL, RPL14, RPL16, RPL2, RPL20, RPL36, RPS11, RPS12, RPS12\_3END, RPS14, RPS19, RPS2, RPS7*, and *RRN16*. The pan genome of the whole considered species, for its part, contains 268 genes. Note that, according to our computation, no gene was specific to a given clade (that is, present in only one clade).

  ----------------- --------------------- --------- -------------- -------------- --------------
  *Taxonomy*                                 Nb.       Min N.b        Max N.b        Avg N.b
                                           genomes   of pan genes   of pan genes   of pan genes
  *Alveolata*       *Chromerida*              2          253            265           259.0
                    *Dinophyceae*             2          265            266           265.5
  *Cryptophyta*     *Pyrenomonadales*         2          258            259           258.5
  *Euglenozoa*      *Euglenida*               7          193            267          253.428
  *Haptophyceae*    *Phaeocystales*           1          266            266           266.0
                    *Isochrysidales*          1          251            251           251.0
                    *Pavlovales*              1          258            258           258.0
  *Rhodophyta*      *Bangiophyceae*           6          156            266          240.166
                    *Florideophyceae*         3          251            267          258.333
  *Stramenopiles*   *Px\_clade*               6          251            271          261.166
                    *Bacillariophyta*        20          138            271           231.35
                    *Eustigmatophyceae*       6          253            267           262.16
                    *Raphidophyceae*          1          258            258           258.0
                    *Pelagophyceae*           2           73            266           169.5
  *Viridiplantae*   *Chlorophyta*            58          156            271          244.517
                    *Streptophyta*           717          85            271          228.638
  ----------------- --------------------- --------- -------------- -------------- --------------

Relations between gene content and phylogeny
--------------------------------------------

We then have further investigated the distribution of number of genes according to the group of species. Obtained results are reproduced in Figures \[fig:genes\] and \[fig:pan\_genomes\]. Four groups have appeared among the 845 genomes, which are taxonomically coherent. As shown in Fig. \[fig:pan\_genomes\], the cluster of largest genomes has a number of genes ranging from 229 to 271, while in the group of smallest genomes, the lowest number of genes is for the *Viridiplantae* case. In particular, among the genomes having less than 120 genes, we found accession number NC\_012903.1 (*Eukaryota, Stramenopiles, Pelagophyceae, Pelagomonadales, Aureoumbra lagunensis*), and 63 *Spermatophyta* species: 3 *Pinidae*, 58 *Magnoliophyta*, one *Cycadidae*, and finally one *Gnetidae*. We finally obtain chloroplast genomes varying from 73 to 271 genes.

![Classification of chloroplast genomes according to numbers of pan genes.\[fig:pan\_genomes\]](figure_2.png){width="50.00000%"}

We can further note that (1) most of the organisms in green lineage (green algae and land plants) have a lower number of genes in their chloroplasts compared to the red algae. (2) Most land plants have genome sizes ranging between 120 and 160 kb [@green2011chloroplast]. (3) Most of the differences in genome size are due to the number of paralogous genes.

When regarding more deeply the ordered list of genes to investigate the reasons of such differences of size, it appears to us that the gene content evolution can mostly be explained by repetitions of some genes and the loss of other ones: no large scale recombination is responsible of such variations. Usual case is as in Figure \[fig:ACCApan\] for ACCA pan gene, on which single vulnerable genes are lost, possibly in various independent branches, due to deletere mutations. Such results have been obtained by comparing, for each couple of close genomes, all gene names and positions, by practicing a naked eye investigation using homemade scripts. Some mutation and indel events are provided too in Table \[my-label\], for the sake of illustration.

Conclusion {#Conclusion}
==========

In this article, we made significant progress in the study of chloroplastic sequence evolution, by providing material and methods required in the quest of the ancestral genome of the chloroplasts. A large set of complete chloroplast genomes has been studied *de novo* regarding both core and pan genomes, phylogenetic relationship, and gene content modifications. We then started to study the produced data, by emphasizing some remarkable relations between well-known events of the chloroplast history and the evolution of gene contents over the phylogenetic tree.

![image](ACCApan)

In future work, our intention is to investigate more systematically such relations between remarkable ancestral nodes in the tree, endosymbiosis events, and evolution of gene content. We will wonder whether some branches of the trees are statistically remarkable when considering gene content (for instance, do we have a correlation between the presence or absence of a subset of genes, and a particular taxonomy). Then, the gene ordering and content of each ancestral node will be computed using ad hoc algorithms, ancestral DNA sequences will be inferred, and ancestral intergenic regions will be deduced, in order to have all ancestral genomes with confidence indications like probabilities. The produced ancestral genomes will then be used to investigate hypotheses formulated by biologists, regarding the origin of chloroplasts, their recombination events, and the transfer of some material to the nucleus. We will in particular study whether recombination events where uniform over time and on the whole sequence, or if it is possible to highlight some hot spots of recombination in the history of these chloroplasts.

*All computations have been performed using the “Mésocentre de calcul de l’Université de Franche-Comté” supercomputer facilities.*

[^1]: [red]{}All data are available at...