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  1. Article ; Online: Comparative characterization of the infant gut microbiome and their maternal lineage by a multi-omics approach.

    Barker-Tejeda, Tomás Clive / Zubeldia-Varela, Elisa / Macías-Camero, Andrea / Alonso, Lola / Martín-Antoniano, Isabel Adoración / Rey-Stolle, María Fernanda / Mera-Berriatua, Leticia / Bazire, Raphaëlle / Cabrera-Freitag, Paula / Shanmuganathan, Meera / Britz-McKibbin, Philip / Ubeda, Carles / Francino, M Pilar / Barber, Domingo / Ibáñez-Sandín, María Dolores / Barbas, Coral / Pérez-Gordo, Marina / Villaseñor, Alma

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 3004

    Abstract: The human gut microbiome establishes and matures during infancy, and dysregulation at this stage may lead to pathologies later in life. We conducted a multi-omics study comprising three generations of family members to investigate the early development ... ...

    Abstract The human gut microbiome establishes and matures during infancy, and dysregulation at this stage may lead to pathologies later in life. We conducted a multi-omics study comprising three generations of family members to investigate the early development of the gut microbiota. Fecal samples from 200 individuals, including infants (0-12 months old; 55% females, 45% males) and their respective mothers and grandmothers, were analyzed using two independent metabolomics platforms and metagenomics. For metabolomics, gas chromatography and capillary electrophoresis coupled to mass spectrometry were applied. For metagenomics, both 16S rRNA gene and shotgun sequencing were performed. Here we show that infants greatly vary from their elders in fecal microbiota populations, function, and metabolome. Infants have a less diverse microbiota than adults and present differences in several metabolite classes, such as short- and branched-chain fatty acids, which are associated with shifts in bacterial populations. These findings provide innovative biochemical insights into the shaping of the gut microbiome within the same generational line that could be beneficial in improving childhood health outcomes.
    MeSH term(s) Infant ; Male ; Adult ; Female ; Humans ; Child ; Aged ; Infant, Newborn ; Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 16S/metabolism ; Multiomics ; Metabolome ; Feces/microbiology ; Mothers
    Chemical Substances RNA, Ribosomal, 16S
    Language English
    Publishing date 2024-04-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47182-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Challenges in the Integration of Omics and Non-Omics Data.

    López de Maturana, Evangelina / Alonso, Lola / Alarcón, Pablo / Martín-Antoniano, Isabel Adoración / Pineda, Silvia / Piorno, Lucas / Calle, M Luz / Malats, Núria

    Genes

    2019  Volume 10, Issue 3

    Abstract: Omics data integration is already a reality. However, few omics-based algorithms show enough predictive ability to be implemented into clinics or public health domains. Clinical/epidemiological data tend to explain most of the variation of health-related ...

    Abstract Omics data integration is already a reality. However, few omics-based algorithms show enough predictive ability to be implemented into clinics or public health domains. Clinical/epidemiological data tend to explain most of the variation of health-related traits, and its joint modeling with omics data is crucial to increase the algorithm's predictive ability. Only a small number of published studies performed a "real" integration of omics and non-omics (OnO) data, mainly to predict cancer outcomes. Challenges in OnO data integration regard the nature and heterogeneity of non-omics data, the possibility of integrating large-scale non-omics data with high-throughput omics data, the relationship between OnO data (i.e., ascertainment bias), the presence of interactions, the fairness of the models, and the presence of subphenotypes. These challenges demand the development and application of new analysis strategies to integrate OnO data. In this contribution we discuss different attempts of OnO data integration in clinical and epidemiological studies. Most of the reviewed papers considered only one type of omics data set, mainly RNA expression data. All selected papers incorporated non-omics data in a low-dimensionality fashion. The integrative strategies used in the identified papers adopted three modeling methods: Independent, conditional, and joint modeling. This review presents, discusses, and proposes integrative analytical strategies towards OnO data integration.
    MeSH term(s) Algorithms ; Computational Biology/methods ; Genetic Predisposition to Disease ; Genomics ; Humans ; Models, Genetic ; Prognosis ; Quantitative Trait Loci ; Sequence Analysis, RNA
    Language English
    Publishing date 2019-03-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes10030238
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.

    Obeso, David / Mera-Berriatua, Leticia / Rodríguez-Coira, Juan / Rosace, Domenico / Fernández, Paloma / Martín-Antoniano, Isabel Adoración / Santaolalla, Marcela / Marco Martín, Guadalupe / Chivato, Tomás / Fernández-Rivas, Montserrat / Ramos, Tania / Blanco, Carlos / Alvarado, María I / Domínguez, Carmen / Angulo, Santiago / Barbas, Coral / Barber, Domingo / Villaseñor, Alma / Escribese, María M

    Allergy

    2018  Volume 73, Issue 11, Page(s) 2137–2149

    Abstract: Background: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin ... ...

    Abstract Background: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics.
    Methods: Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis.
    Results: We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism.
    Conclusion: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.
    MeSH term(s) Biomarkers ; Blood Platelets/metabolism ; Bronchial Hyperreactivity/diagnosis ; Bronchial Hyperreactivity/etiology ; Bronchial Hyperreactivity/metabolism ; Chromatography, Liquid ; Computational Biology/methods ; Female ; Food/adverse effects ; Food Hypersensitivity/diagnosis ; Food Hypersensitivity/etiology ; Food Hypersensitivity/metabolism ; Gas Chromatography-Mass Spectrometry ; Gene Expression Profiling ; Genomics/methods ; Humans ; Male ; Mass Spectrometry ; Metabolome ; Metabolomics/methods ; Phenotype ; Severity of Illness Index
    Chemical Substances Biomarkers
    Language English
    Publishing date 2018-08-09
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.13563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.

    López de Maturana, Evangelina / Rodríguez, Juan Antonio / Alonso, Lola / Lao, Oscar / Molina-Montes, Esther / Martín-Antoniano, Isabel Adoración / Gómez-Rubio, Paulina / Lawlor, Rita / Carrato, Alfredo / Hidalgo, Manuel / Iglesias, Mar / Molero, Xavier / Löhr, Matthias / Michalski, Christopher / Perea, José / O'Rorke, Michael / Barberà, Victor Manuel / Tardón, Adonina / Farré, Antoni /
    Muñoz-Bellvís, Luís / Crnogorac-Jurcevic, Tanja / Domínguez-Muñoz, Enrique / Gress, Thomas / Greenhalf, William / Sharp, Linda / Arnes, Luís / Cecchini, Lluís / Balsells, Joaquim / Costello, Eithne / Ilzarbe, Lucas / Kleeff, Jörg / Kong, Bo / Márquez, Mirari / Mora, Josefina / O'Driscoll, Damian / Scarpa, Aldo / Ye, Weimin / Yu, Jingru / García-Closas, Montserrat / Kogevinas, Manolis / Rothman, Nathaniel / Silverman, Debra T / Albanes, Demetrius / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Brennan, Paul / Bueno-de-Mesquita, Bas / Buring, Julie / Canzian, Federico / Du, Margaret / Gallinger, Steve / Gaziano, J Michael / Goodman, Phyllis J / Gunter, Marc / LeMarchand, Loic / Li, Donghui / Neale, Rachael E / Peters, Ulrika / Petersen, Gloria M / Risch, Harvey A / Sánchez, Maria José / Shu, Xiao-Ou / Thornquist, Mark D / Visvanathan, Kala / Zheng, Wei / Chanock, Stephen J / Easton, Douglas / Wolpin, Brian M / Stolzenberg-Solomon, Rachael Z / Klein, Alison P / Amundadottir, Laufey T / Marti-Renom, Marc A / Real, Francisco X / Malats, Núria

    Genome medicine

    2021  Volume 13, Issue 1, Page(s) 15

    Abstract: Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance.: ... ...

    Abstract Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance.
    Methods: We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants.
    Results: We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support.
    Conclusions: This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.
    MeSH term(s) Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Computer Simulation ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Genome, Human ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium/genetics ; Pancreatic Neoplasms/genetics ; Reproducibility of Results ; Signal Transduction/genetics
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2021-02-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-020-00816-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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