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  1. Article ; Online: Should we really use graph neural networks for transcriptomic prediction?

    Brouard, Céline / Mourad, Raphaël / Vialaneix, Nathalie

    Briefings in bioinformatics

    2024  Volume 25, Issue 2

    Abstract: The recent development of deep learning methods have undoubtedly led to great improvement in various machine learning tasks, especially in prediction tasks. This type of methods have also been adapted to answer various problems in bioinformatics, ... ...

    Abstract The recent development of deep learning methods have undoubtedly led to great improvement in various machine learning tasks, especially in prediction tasks. This type of methods have also been adapted to answer various problems in bioinformatics, including automatic genome annotation, artificial genome generation or phenotype prediction. In particular, a specific type of deep learning method, called graph neural network (GNN) has repeatedly been reported as a good candidate to predict phenotypes from gene expression because its ability to embed information on gene regulation or co-expression through the use of a gene network. However, up to date, no complete and reproducible benchmark has ever been performed to analyze the trade-off between cost and benefit of this approach compared to more standard (and simpler) machine learning methods. In this article, we provide such a benchmark, based on clear and comparable policies to evaluate the different methods on several datasets. Our conclusion is that GNN rarely provides a real improvement in prediction performance, especially when compared to the computation effort required by the methods. Our findings on a limited but controlled simulated dataset shows that this could be explained by the limited quality or predictive power of the input biological gene network itself.
    MeSH term(s) Gene Expression Profiling ; Transcriptome ; Benchmarking ; Computational Biology ; Neural Networks, Computer
    Language English
    Publishing date 2024-02-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbae027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Feature selection for kernel methods in systems biology.

    Brouard, Céline / Mariette, Jérôme / Flamary, Rémi / Vialaneix, Nathalie

    NAR genomics and bioinformatics

    2022  Volume 4, Issue 1, Page(s) lqac014

    Abstract: The substantial development of high-throughput biotechnologies has rendered large-scale multi-omics datasets increasingly available. New challenges have emerged to process and integrate this large volume of information, often obtained from widely ... ...

    Abstract The substantial development of high-throughput biotechnologies has rendered large-scale multi-omics datasets increasingly available. New challenges have emerged to process and integrate this large volume of information, often obtained from widely heterogeneous sources. Kernel methods have proven successful to handle the analysis of different types of datasets obtained on the same individuals. However, they usually suffer from a lack of interpretability since the original description of the individuals is lost due to the kernel embedding. We propose novel feature selection methods that are adapted to the kernel framework and go beyond the well-established work in supervised learning by addressing the more difficult tasks of unsupervised learning and kernel output learning. The method is expressed under the form of a non-convex optimization problem with a ℓ
    Language English
    Publishing date 2022-03-07
    Publishing country England
    Document type Journal Article
    ISSN 2631-9268
    ISSN (online) 2631-9268
    DOI 10.1093/nargab/lqac014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial.

    Gaborit, Benjamin / Vanhove, Bernard / Lacombe, Karine / Guimard, Thomas / Hocqueloux, Laurent / Perrier, Ludivine / Dubee, Vincent / Ferre, Virginie / Bressollette, Celine / Josien, Régis / Thuaut, Aurélie Le / Vibet, Marie-Anne / Jobert, Alexandra / Dailly, Eric / Ader, Florence / Brouard, Sophie / Duvaux, Odile / Raffi, François

    Open forum infectious diseases

    2023  Volume 10, Issue 11, Page(s) ofad525

    Abstract: Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).: Methods: This phase 2b clinical trial enrolled ... ...

    Abstract Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).
    Methods: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15.
    Results: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66;
    Conclusions: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.
    Language English
    Publishing date 2023-10-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofad525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Improved Small Molecule Identification through Learning Combinations of Kernel Regression Models.

    Brouard, Céline / Bassé, Antoine / d'Alché-Buc, Florence / Rousu, Juho

    Metabolites

    2019  Volume 9, Issue 8

    Abstract: In small molecule identification from tandem mass (MS/MS) spectra, input-output kernel regression (IOKR) currently provides the state-of-the-art combination of fast training and prediction and high identification rates. The IOKR approach can be simply ... ...

    Abstract In small molecule identification from tandem mass (MS/MS) spectra, input-output kernel regression (IOKR) currently provides the state-of-the-art combination of fast training and prediction and high identification rates. The IOKR approach can be simply understood as predicting a fingerprint vector from the MS/MS spectrum of the unknown molecule, and solving a pre-image problem to find the molecule with the most similar fingerprint. In this paper, we bring forward the following improvements to the IOKR framework: firstly, we formulate the IOKRreverse model that can be understood as mapping molecular structures into the MS/MS feature space and solving a pre-image problem to find the molecule whose predicted spectrum is the closest to the input MS/MS spectrum. Secondly, we introduce an approach to combine several IOKR and IOKRreverse models computed from different input and output kernels, called IOKRfusion. The method is based on minimizing structured Hinge loss of the combined model using a mini-batch stochastic subgradient optimization. Our experiments show a consistent improvement of top-k accuracy both in positive and negative ionization mode data.
    Language English
    Publishing date 2019-08-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo9080160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Fast metabolite identification with Input Output Kernel Regression

    Brouard, Céline / Shen, Huibin / Dührkop, Kai / d'Alché-Buc, Florence / Böcker, Sebastian / Rousu, Juho

    Bioinformatics. 2016 June 15, v. 32, no. 12

    2016  

    Abstract: ... Contact: celine.brouard@aalto.fi Supplementary information: Supplementary data are available ...

    Abstract Motivation: An important problematic of metabolomics is to identify metabolites using tandem mass spectrometry data. Machine learning methods have been proposed recently to solve this problem by predicting molecular fingerprint vectors and matching these fingerprints against existing molecular structure databases. In this work we propose to address the metabolite identification problem using a structured output prediction approach. This type of approach is not limited to vector output space and can handle structured output space such as the molecule space. Results: We use the Input Output Kernel Regression method to learn the mapping between tandem mass spectra and molecular structures. The principle of this method is to encode the similarities in the input (spectra) space and the similarities in the output (molecule) space using two kernel functions. This method approximates the spectra-molecule mapping in two phases. The first phase corresponds to a regression problem from the input space to the feature space associated to the output kernel. The second phase is a preimage problem, consisting in mapping back the predicted output feature vectors to the molecule space. We show that our approach achieves state-of-the-art accuracy in metabolite identification. Moreover, our method has the advantage of decreasing the running times for the training step and the test step by several orders of magnitude over the preceding methods. Availability and implementation : Contact: celine.brouard@aalto.fi Supplementary information: Supplementary data are available at Bioinformatics online.
    Keywords artificial intelligence ; bioinformatics ; chemical structure ; databases ; metabolites ; metabolomics ; prediction ; regression analysis ; tandem mass spectrometry
    Language English
    Dates of publication 2016-0615
    Size p. i28-i36.
    Publishing place Oxford University Press
    Document type Article
    ZDB-ID 1468345-3
    ISSN 1460-2059 ; 1367-4811 ; 1367-4803
    ISSN (online) 1460-2059 ; 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btw246
    Database NAL-Catalogue (AGRICOLA)

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  6. Book ; Online: Learning to Predict Graphs with Fused Gromov-Wasserstein Barycenters

    Brogat-Motte, Luc / Flamary, Rémi / Brouard, Céline / Rousu, Juho / d'Alché-Buc, Florence

    2022  

    Abstract: This paper introduces a novel and generic framework to solve the flagship task of supervised labeled graph prediction by leveraging Optimal Transport tools. We formulate the problem as regression with the Fused Gromov-Wasserstein (FGW) loss and propose a ...

    Abstract This paper introduces a novel and generic framework to solve the flagship task of supervised labeled graph prediction by leveraging Optimal Transport tools. We formulate the problem as regression with the Fused Gromov-Wasserstein (FGW) loss and propose a predictive model relying on a FGW barycenter whose weights depend on inputs. First we introduce a non-parametric estimator based on kernel ridge regression for which theoretical results such as consistency and excess risk bound are proved. Next we propose an interpretable parametric model where the barycenter weights are modeled with a neural network and the graphs on which the FGW barycenter is calculated are additionally learned. Numerical experiments show the strength of the method and its ability to interpolate in the labeled graph space on simulated data and on a difficult metabolic identification problem where it can reach very good performance with very little engineering.
    Keywords Statistics - Machine Learning ; Computer Science - Machine Learning
    Subject code 006
    Publishing date 2022-02-08
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Liquid-chromatography retention order prediction for metabolite identification.

    Bach, Eric / Szedmak, Sandor / Brouard, Céline / Böcker, Sebastian / Rousu, Juho

    Bioinformatics (Oxford, England)

    2018  Volume 34, Issue 17, Page(s) i875–i883

    Abstract: Motivation: Liquid Chromatography (LC) followed by tandem Mass Spectrometry (MS/MS) is one of the predominant methods for metabolite identification. In recent years, machine learning has started to transform the analysis of tandem mass spectra and the ... ...

    Abstract Motivation: Liquid Chromatography (LC) followed by tandem Mass Spectrometry (MS/MS) is one of the predominant methods for metabolite identification. In recent years, machine learning has started to transform the analysis of tandem mass spectra and the identification of small molecules. In contrast, LC data is rarely used to improve metabolite identification, despite numerous published methods for retention time prediction using machine learning.
    Results: We present a machine learning method for predicting the retention order of molecules; that is, the order in which molecules elute from the LC column. Our method has important advantages over previous approaches: We show that retention order is much better conserved between instruments than retention time. To this end, our method can be trained using retention time measurements from different LC systems and configurations without tedious pre-processing, significantly increasing the amount of available training data. Our experiments demonstrate that retention order prediction is an effective way to learn retention behaviour of molecules from heterogeneous retention time data. Finally, we demonstrate how retention order prediction and MS/MS-based scores can be combined for more accurate metabolite identifications when analyzing a complete LC-MS/MS run.
    Availability and implementation: Implementation of the method is available at https://version.aalto.fi/gitlab/bache1/retention_order_prediction.git.
    MeSH term(s) Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods
    Language English
    Publishing date 2018-11-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/bty590
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Long-term evolution of neuroendocrine cell hyperplasia of infancy: the FRENCHI findings.

    Dervaux, Morgane / Thumerelle, Caroline / Fabre, Candice / Abou-Taam, Rola / Bihouee, Tiphaine / Brouard, Jacques / Clement, Annick / Delacourt, Christophe / Delestrain, Céline / Epaud, Ralph / Ghdifan, Sofiane / Hadchouel, Alice / Houdouin, Véronique / Labouret, Géraldine / Perisson, Caroline / Reix, Philippe / Renoux, Marie-Catherine / Troussier, Françoise / Weiss, Laurence /
    Mazenq, Julie / Nathan, Nadia / Dubus, Jean-Christophe

    European journal of pediatrics

    2022  Volume 182, Issue 2, Page(s) 949–956

    Abstract: Only few studies report long-term evolution of patients with neuroendocrine cell hyperplasia of infancy (NEHI). We report data from a 54-patient cohort followed up in the French network for rare respiratory diseases (RespiRare). Demographic ... ...

    Abstract Only few studies report long-term evolution of patients with neuroendocrine cell hyperplasia of infancy (NEHI). We report data from a 54-patient cohort followed up in the French network for rare respiratory diseases (RespiRare). Demographic characteristics and respiratory and nutritional evolution were collected at the time of the patient's last scheduled visit. The mean duration of follow-up was 68 months (5 months to 18 years). Fifteen patients (27.8%) were considered clinically cured. During follow-up, hospitalizations for wheezy exacerbations were reported in 35 patients (55%), and asthma diagnosed in 20 (37%). Chest CT scan improvement was noted in 25/44 (56.8%). Spirometry showed a persistent obstructive syndrome in 8/27 (29.6%). A sleep disorder was rare (2/36, 5.5%). Oxygen weaning occurred in 28 of the 45 patients initially treated (62.2%) and was age-dependent (35.7% under 2 years, 70.5% between 2 and 6 years, and 100% after 7 years). Oxygen duration was linked to a biopsy-proven diagnosis (p = 0.02) and to the use of a nutritional support (p = 0.003). Corticosteroids were largely prescribed at diagnosis, with no evident respiratory or nutritional effect during follow-up. Among 23 patients with an initial failure to thrive, 12 (52.2%) had no weight recovery. Initial enteral feeding (17/54, 31.5%) was stopped at a mean age of 43 months (3 to 120), with no effect on cure and oxygen liberation at the last visit.  Conclusion: Our results show that NEHI has a globally positive, but unequal, improvement over time. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI. What is Known: • Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose long-term outcome is considered positive from very few studies including heterogeneous populations. What is New: • The 68-month follow-up of our 54-patient cohort showed respiratory/nutritional symptom persistence in 72.2%, oxygen requiring in 34%, and asthma in 37%. When controlled, radiological or functional improvement was noted in 56.8 and 40.7%. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI.
    MeSH term(s) Humans ; Infant ; Child, Preschool ; Adult ; Hyperplasia/pathology ; Neuroendocrine Cells/pathology ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/therapy ; Oxygen ; Asthma/diagnosis ; Asthma/epidemiology ; Asthma/therapy ; Rare Diseases
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2022-11-30
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 194196-3
    ISSN 1432-1076 ; 0340-6199 ; 0943-9676
    ISSN (online) 1432-1076
    ISSN 0340-6199 ; 0943-9676
    DOI 10.1007/s00431-022-04734-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management.

    Fabre, Candice / Thumerelle, Caroline / Dervaux, Morgane / Abou-Taam, Rola / Bihouee, Tiphaine / Brouard, Jacques / Clement, Annick / Delacourt, Christophe / Delestrain, Céline / Epaud, Ralph / Ghdifan, Sofiane / Hadchouel, Alice / Houdouin, Véronique / Labouret, Géraldine / Perisson, Caroline / Reix, Philippe / Renoux, Marie-Catherine / Troussier, Françoise / Weiss, Laurence /
    Mazenq, Julie / Nathan, Nadia / Dubus, Jean-Christophe

    European journal of pediatrics

    2022  Volume 181, Issue 8, Page(s) 3067–3073

    Abstract: Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current ... ...

    Abstract Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%).
    Conclusion: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs.
    What is known: •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy.
    What is new: •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.
    MeSH term(s) Child ; Humans ; Hyperplasia/diagnosis ; Infant ; Infant, Newborn ; Lung/diagnostic imaging ; Lung/pathology ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/therapy ; Male ; Neuroendocrine Cells/pathology ; Rare Diseases ; Retrospective Studies
    Language English
    Publishing date 2022-06-09
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 194196-3
    ISSN 1432-1076 ; 0340-6199 ; 0943-9676
    ISSN (online) 1432-1076
    ISSN 0340-6199 ; 0943-9676
    DOI 10.1007/s00431-022-04510-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Gene regulatory network inference methodology for genomic and transcriptomic data acquired in genetically related heterozygote individuals.

    Pomiès, Lise / Brouard, Céline / Duruflé, Harold / Maigné, Élise / Carré, Clément / Gody, Louise / Trösser, Fulya / Katsirelos, George / Mangin, Brigitte / Langlade, Nicolas B / de Givry, Simon

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 17, Page(s) 4127–4134

    Abstract: Motivation: Inferring gene regulatory networks in non-independent genetically related panels is a methodological challenge. This hampers evolutionary and biological studies using heterozygote individuals such as in wild sunflower populations or ... ...

    Abstract Motivation: Inferring gene regulatory networks in non-independent genetically related panels is a methodological challenge. This hampers evolutionary and biological studies using heterozygote individuals such as in wild sunflower populations or cultivated hybrids.
    Results: First, we simulated 100 datasets of gene expressions and polymorphisms, displaying the same gene expression distributions, heterozygosities and heritabilities as in our dataset including 173 genes and 353 genotypes measured in sunflower hybrids. Secondly, we performed a meta-analysis based on six inference methods [least absolute shrinkage and selection operator (Lasso), Random Forests, Bayesian Networks, Markov Random Fields, Ordinary Least Square and fast inference of networks from directed regulation (Findr)] and selected the minimal density networks for better accuracy with 64 edges connecting 79 genes and 0.35 area under precision and recall (AUPR) score on average. We identified that triangles and mutual edges are prone to errors in the inferred networks. Applied on classical datasets without heterozygotes, our strategy produced a 0.65 AUPR score for one dataset of the DREAM5 Systems Genetics Challenge. Finally, we applied our method to an experimental dataset from sunflower hybrids. We successfully inferred a network composed of 105 genes connected by 106 putative regulations with a major connected component.
    Availability and implementation: Our inference methodology dedicated to genomic and transcriptomic data is available at https://forgemia.inra.fr/sunrise/inference_methods.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Humans ; Gene Regulatory Networks ; Transcriptome ; Heterozygote ; Bayes Theorem ; Genomics ; Algorithms
    Language English
    Publishing date 2022-05-28
    Publishing country England
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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