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The pan-cancer pathological regulatory landscape

Matias M. Falco, Marta Bleda, José Carbonell-Caballero, Joaquín Dopazo
2016 Scientific Reports  
Figure 4 . 4 K-M plots representing TF activities significantly associated to patient survival.  ...  The fifth column contains the number of TFs significant in the K-M analysis. TFs in bold are significant with an adjusted p-value < 0.05.  ... 
doi:10.1038/srep39709 pmid:28000771 pmcid:PMC5175166 fatcat:adgulr53uzhm7duu7cvotuvhre

Mechanistic modeling of the SARS-CoV-2 disease map [article]

Kinza Rian, Marina Esteban-Medina, Marta R Hidalgo, Cankut Cubuk, Matias M Falco, Carlos Loucera, Devrim Gunyel, Marek Ostaszewski, Maria Pena-Chilet, Joaquin Dopazo
2020 bioRxiv   pre-print
Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map in which the detailed activity of the human signaling circuits related to the viral infection and the different antiviral responses, including immune and inflammatory activities, can be inferred from gene expression experiments. Moreover, given to the mechanistic properties of the model, the effect of potential interventions, such as knock-downs, over-expression or drug effects
more » ... tly the system models the effect of more than 8000 DrugBank drugs) can be studied in specific conditions. This tool, with the holistic, systems biology approach to the understanding of the complexities of the viral infection process, will become an important asset in the search for efficient antiviral treatments. The tool is freely available at: http://hipathia.babelomics.org/covid19/.
doi:10.1101/2020.04.12.025577 fatcat:ydzmqqcldrcxjh6t7jvvc2ihse

Mechanistic models of signaling pathways deconvolute the glioblastoma single-cell functional landscape

Matías M Falco, María Peña-Chilet, Carlos Loucera, Marta R Hidalgo, Joaquín Dopazo
2020 NAR Cancer  
Single-cell RNA sequencing is revealing an unexpectedly large degree of heterogeneity in gene expression levels across cell populations. However, little is known on the functional consequences of this heterogeneity and the contribution of individual cell fate decisions to the collective behavior of the tissues these cells are part of. Here, we use mechanistic modeling of signaling circuits, which reveals a complex functional landscape at single-cell level. Different clusters of neoplastic
more » ... astoma cells have been defined according to their differences in signaling circuit activity profiles triggering specific cancer hallmarks, which suggest different functional strategies with distinct degrees of aggressiveness. Moreover, mechanistic modeling of effects of targeted drug inhibitions at single-cell level revealed, how in some cells, the substitution of VEGFA, the target of bevacizumab, by other expressed proteins, like PDGFD, KITLG and FGF2, keeps the VEGF pathway active, insensitive to the VEGFA inhibition by the drug. Here, we describe for the first time mechanisms that individual cells use to avoid the effect of a targeted therapy, providing an explanation for the innate resistance to the treatment displayed by some cells. Our results suggest that mechanistic modeling could become an important asset for the definition of personalized therapeutic interventions.
doi:10.1093/narcan/zcaa011 fatcat:6kbtq2ztx5fcpd2lfmsmxohita

Mechanistic models of signaling pathways deconvolute the functional landscape of glioblastoma at single cell resolution

Matías M. Falco, María Peña-Chilet, Carlos Loucera, Marta R. Hidalgo, Joaquín Dopazo
2019 biorxiv/medrxiv  
The rapid development of single cell RNA-sequencing (scRNA-seq) technologies is revealing an unexpectedly large degree of heterogeneity in gene expression levels across the different cells that compose the same tissue sample. However, little is known on the functional consequences of this heterogeneity and the contribution of individual cell-fate decisions to the collective behavior of the tissues these cells are part of. Mechanistic models of signaling pathways have already proven to be useful
more » ... tools for understanding relevant aspects of cell functionality. Here we propose to use this mechanistic modeling strategy to deconvolute the complexity of the functional behavior of a tissue by dissecting it into the individual functional landscapes of its component cells by using a single-cell RNA-seq experiment of glioblastoma cells. This mechanistic modeling analysis revealed a high degree of heterogeneity at the scale of signaling circuits, suggesting the existence of a complex functional landscape at single cell level. Different clusters of neoplastic glioblastoma cells have been characterized according to their differences in signaling circuit activity profiles, which only partly overlap with the conventional glioblastoma subtype classification. The activity of signaling circuits that trigger cell functionalities which can easily be assimilated to cancer hallmarks reveals different functional strategies with different degrees of aggressiveness followed by any of the clusters. In addition, mechanistic modeling allows simulating the effect of interventions on the components of the signaling circuits, such as drug inhibitions. Thus, effects of drug inhibitions at single cell level can be dissected, revealing for the first time the mechanisms that individual cells use to avoid the effect of a targeted therapy which explain why and how a small proportion of cells display, in fact, different degrees of resistance to the treatment. The results presented here strongly suggest that mechanistic modeling at single cell level no [...]
doi:10.1101/858811 fatcat:ksncb2euoffk5ccm5orj2vi5ci

Using mechanistic models for the clinical interpretation of complex genomic variation

María Peña-Chilet, Marina Esteban-Medina, Matias M. Falco, Kinza Rian, Marta R. Hidalgo, Carlos Loucera, Joaquín Dopazo
2019 Scientific Reports  
RNA-seq gene expression data were normalized with the Trimmed mean of M values (TMM) normalization method using the edgeR package 87 .  ... 
doi:10.1038/s41598-019-55454-7 pmid:31831811 pmcid:PMC6908734 fatcat:n6tnv6vm3behnfl27ksrlg5y3q

Mechanistic modeling of the SARS-CoV-2 disease map

Kinza Rian, Marina Esteban-Medina, Marta R. Hidalgo, Cankut Çubuk, Matias M. Falco, Carlos Loucera, Devrim Gunyel, Marek Ostaszewski, María Peña-Chilet, Joaquín Dopazo
2021 BioData Mining  
AbstractHere we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map. In this framework, the detailed activity of the human signaling circuits related to the viral infection, covering from the entry and replication mechanisms to the downstream consequences as inflammation and antigenic response, can be inferred from gene expression experiments. Moreover, the effect of potential interventions, such as knock-downs, or drug effects (currently the
more » ... ystem models the effect of more than 8000 DrugBank drugs) can be studied. This freely available tool not only provides an unprecedentedly detailed view of the mechanisms of viral invasion and the consequences in the cell but has also the potential of becoming an invaluable asset in the search for efficient antiviral treatments.
doi:10.1186/s13040-021-00234-1 pmid:33478554 fatcat:gz6hyhjzlfbq3oxekedbfzhjp4

Drug repurposing for SARS-CoV-2 infection using machine learning and mechanistic models of the COVID-19 Disease Maps

Carlos Loucera, Marina Esteban-Medina, Kinza Rian, Matías M Falco, Joaquín Dopazo, María Peña-Chilet
2020 Zenodo  
In this work, we use an innovative methodology that combines mechanistic modeling of the signal transduction circuits related to SARS-CoV-2 infection (the COVID-19 disease map) with a machine learning algorithm that learns potential causal interactions between proteins, already targets of drugs, and specific signaling circuits in the COVID-19 disease map, to suggest potentially repurposable drugs.
doi:10.5281/zenodo.4266057 fatcat:ngukcccd3vgzfglnfrhj2xxoti

miQC: An adaptive probabilistic framework for quality control of single-cell RNA-sequencing data

Ariel A. Hippen, Matias M. Falco, Lukas M. Weber, Erdogan Pekcan Erkan, Kaiyang Zhang, Jennifer Anne Doherty, Anna Vähärautio, Casey S. Greene, Stephanie C. Hicks, Magnus Rattray
2021 PLoS Computational Biology  
Cell suspensions were passed through a 70μm cell strainer to remove cell clusters and debris and centrifuged at 300 x g.  ... 
doi:10.1371/journal.pcbi.1009290 pmid:34428202 pmcid:PMC8415599 fatcat:orzotfpo7jczdb57veslhfd4vy

Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection

Carlos Loucera, Marina Esteban-Medina, Kinza Rian, Matías M. Falco, Joaquín Dopazo, María Peña-Chilet
2020 Signal Transduction and Targeted Therapy  
doi:10.1038/s41392-020-00417-y pmid:33311438 fatcat:qpwy2reknvd6jk6ylaalgwhfxm

Genome-scale mechanistic modeling of signaling pathways made easy: a Bioconductor / cytoscape / web server framework for the analysis of omic data

Kinza Rian, Marta R. Hidalgo, Cankut Çubuk, Matias M. Falco, Carlos Loucera, Marina Esteban-Medina, Inmaculada Alamo-Alvarez, María Peña-Chilet, Joaquín Dopazo
2021 Computational and Structural Biotechnology Journal  
Matias M. Falco: Data curation, Validation. Carlos Loucera: Methodology, Formal analysis. Marina Esteban-Medina: Investigation, Data curation.  ... 
doi:10.1016/j.csbj.2021.05.022 pmid:34136096 pmcid:PMC8170118 fatcat:iwh3ib6idngofetlz2t5nfc7ci

Page 31 of The Journal of Animal Ecology Vol. 74, Issue 1 [page]

2005 The Journal of Animal Ecology  
Journal of Animal Ecology 2005 74, 31-40 Productivity and food web structure: association between productivity and link richness among top predators MATIAS ARIM* and FABIAN M.  ...  Since 1987, the diets of the strigiforms Speotyto cunicularia (Burrowing owl), Bubo magellanicus (Magellan horned owl), Glaucidium nanum (Austral pygmy owl), Tyto alba (Barn owl), the falconiform Falco  ... 

Do Transcription Factors Play Special Roles in Adaptive Variation?

C. Martin, N. Ellis, F. Rook
2010 Plant Physiology  
Evandro Novaes, Matias Kirst, Vincent Chiang, Heike Winter-Sederoff, and Ronald Sederoff 555 Enhancing C 3 Photosynthesis. Susanne von Caemmerer and John R.  ...  Yan Liang, Ahmed Faik, Marcia Kieliszewski, Li Tan, Wen-Liang Xu, and Allan M.  ... 
doi:10.1104/pp.110.161331 pmid:20921174 pmcid:PMC2949032 fatcat:ti2i6bo4wrg2bg7k3exwcuk5sy

The Hero in the Lyrical Epic Poem Detvan in the Context of Contemporary Nationalism

Marta Fülöpová
2021 Slovenský Národopis  
Fülöpová, M. 2021.  ...  M at iá š K r á ľ a s oKol M a rt i n Sokolom navodený vzťah Martina a Matiáša je prítomný na viacerých úrovniach textu.  ... 
doi:10.2478/se-2021-0006 fatcat:w5cqq52j3zgorjafnpqbb6d7qe

Galiana: història d'un falcó

Carmel Ferragud, Ricardo Olmos de León, Vicent Bataller
2021 Scripta: Revista Internacional de Literatura i Cultura Medieval i Moderna  
Resum: En 1365 va tenir lloc una disputa davant la cort del governador de Mallorca per la propietat d'un falcó entre els donzells Berenguer de Galiana i Bernat Togores, en la qual es veu involucrat l'ensinistrador  ...  Galiana: història d'un falcó Carmel Ferragud & Ricardo M. Olmos de León & Vicent Bataller. Galiana: història d'un falcó Carmel Ferragud & Ricardo M. Olmos de León & Vicent Bataller.  ...  La dona de Vilamarí, en la seua declaració, afirmava que el falcó deCarmel Ferragud & Ricardo M. Olmos de León & Vicent Bataller. Galiana: història d'un falcó Carmel Ferragud & Ricardo M.  ... 
doi:10.7203/scripta.17.20918 fatcat:ij5e3ghahvdcflaa3eecyvlbvu

PERFIL FITOQUÍMICO E SUSCETIBILIDADE ANTIBACTERIANA DA Lafoensia pacari Saint-Hilaire (LYTHRACEAE) e Persea americana Mill (LAURACEAE) DO CERRADO BRASILEIRO

Alexandra Barbosa da Silva, Nágila Fernanda Moreira Melo, José Ribamar Nogueira, Luciano Nonato Carvalho Martins, Alvaro Carlos Galdos-Riveros
2016 Enciclopédia Biosfera  
O consumo do fruto da Persea americana M. conhecida como abacate serve no tratamento de enfermidades como diabetes, cardiopatias, dislipidemias, hepatopatias e como redutor de colesterol.  ...  TABELA 1 - 1 Composição fitoquímica da Lafoensia pacari e a Persea americana M. : ++++ fortemente positivo, ++ moderadamente positivo, + positivo e -negativo. MATIAS, E. F. F.; SANTOS, K. K.  ...  Desta forma o microrganismo não teria uma das substâncias necessárias para sua sobrevivência (SILVA FILHO & FALCO, 2000) .  ... 
doi:10.18677/encibio_2016b_118 fatcat:abxfr2egkrddlb2i7xa4mzpavm
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