Marina Naval Sanchez
Katholieke Universiteit Leuven
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Featured researches published by Marina Naval Sanchez.
PLOS Computational Biology | 2014
Rekin's Janky; Annelien Verfaillie; Hana Imrichova; Bram Van de Sande; Laura Standaert; Valerie Christiaens; Gert Hulselmans; Koen Herten; Marina Naval Sanchez; Delphine Potier; Dmitry Svetlichnyy; Zeynep Kalender Atak; Mark Fiers; Jean-Christophe Marine; Stein Aerts
Identifying master regulators of biological processes and mapping their downstream gene networks are key challenges in systems biology. We developed a computational method, called iRegulon, to reverse-engineer the transcriptional regulatory network underlying a co-expressed gene set using cis-regulatory sequence analysis. iRegulon implements a genome-wide ranking-and-recovery approach to detect enriched transcription factor motifs and their optimal sets of direct targets. We increase the accuracy of network inference by using very large motif collections of up to ten thousand position weight matrices collected from various species, and linking these to candidate human TFs via a motif2TF procedure. We validate iRegulon on gene sets derived from ENCODE ChIP-seq data with increasing levels of noise, and we compare iRegulon with existing motif discovery methods. Next, we use iRegulon on more challenging types of gene lists, including microRNA target sets, protein-protein interaction networks, and genetic perturbation data. In particular, we over-activate p53 in breast cancer cells, followed by RNA-seq and ChIP-seq, and could identify an extensive up-regulated network controlled directly by p53. Similarly we map a repressive network with no indication of direct p53 regulation but rather an indirect effect via E2F and NFY. Finally, we generalize our computational framework to include regulatory tracks such as ChIP-seq data and show how motif and track discovery can be combined to map functional regulatory interactions among co-expressed genes. iRegulon is available as a Cytoscape plugin from http://iregulon.aertslab.org.
PLOS Biology | 2010
Stein Aerts; Xiao-Jiang Quan; Annelies Claeys; Marina Naval Sanchez; Phillip Tate; Jiekun Yan; Bassem A. Hassan
CisTarget X is a novel computational method that accurately predicts Atonal governed regulatory networks in the retina of the fruit fly.
Cell Reports | 2014
Delphine Potier; Kristofer Davie; Gert Hulselmans; Marina Naval Sanchez; Lotte Haagen; Vân Anh Huynh-Thu; Duygu Koldere; Arzu Celik; Pierre Geurts; Valerie Christiaens; Stein Aerts
Genome control is operated by transcription factors (TFs) controlling their target genes by binding to promoters and enhancers. Conceptually, the interactions between TFs, their binding sites, and their functional targets are represented by gene regulatory networks (GRNs). Deciphering in vivo GRNs underlying organ development in an unbiased genome-wide setting involves identifying both functional TF-gene interactions and physical TF-DNA interactions. To reverse engineer the GRNs of eye development in Drosophila, we performed RNA-seq across 72 genetic perturbations and sorted cell types and inferred a coexpression network. Next, we derived direct TF-DNA interactions using computational motif inference, ultimately connecting 241 TFs to 5,632 direct target genes through 24,926 enhancers. Using this network, we found network motifs, cis-regulatory codes, and regulators of eye development. We validate the predicted target regions of Grainyhead by ChIP-seq and identify this factor as a general cofactor in the eye network, being bound to thousands of nucleosome-free regions.
Methods of Molecular Biology | 2012
Delphine Potier; Zeynep Kalender Atak; Marina Naval Sanchez; Carl Herrmann; Stein Aerts
Gene expression regulation is a fundamental biological process leading to complete organism development by controlling processes like cell type specification and differentiation. The accuracy of this process is -governed by transcription factors (TFs) acting within a complex gene regulatory network. CisTargetX has been developed to enable a user to predict TFs, enhancers, and target genes involved in the regulation of co-expressed genes. It uses a strategy that incorporates the genome-wide prediction of clusters of transcription factor binding sites (TFBSs), starting from a large, unbiased collection of position weight matrices (PWMs) and uses comparative genomics criteria to filter potential TFBS. We describe in this chapter, step-by-step, how to use cisTargetX starting from a set of genes or TF(s) to predict transcriptional targets with their putative binding sites and networks in Drosophila. Next, we illustrate this approach on a particular developmental system, namely, sensory organ development, and identify relevant TFs, DNA regions regulating gene expression, and TF/target gene interactions. CisTargetX is available at http://med.kuleuven.be/lcb/cisTargetX .
Development | 2018
Mariya P. Dobreva; Vanesa Abon Escalona; Kirstie A. Lawson; Marina Naval Sanchez; Ljuba C. Ponomarev; Paulo N. G. Pereira; Agata Stryjewska; Nathan Criem; Danny Huylebroeck; Susana Lopes; Stein Aerts; An Zwijsen
ABSTRACT Upon gastrulation, the mammalian conceptus transforms rapidly from a simple bilayer into a multilayered embryo enveloped by its extra-embryonic membranes. Impaired development of the amnion, the innermost membrane, causes major malformations. To clarify the origin of the mouse amnion, we used single-cell labelling and clonal analysis. We identified four clone types with distinct clonal growth patterns in amniotic ectoderm. Two main types have progenitors in extreme proximal-anterior epiblast. Early descendants initiate and expand amniotic ectoderm posteriorly, while descendants of cells remaining anteriorly later expand amniotic ectoderm from its anterior side. Amniogenesis is abnormal in embryos deficient in the bone morphogenetic protein (BMP) signalling effector SMAD5, with delayed closure of the proamniotic canal, and aberrant amnion and folding morphogenesis. Transcriptomics of individual Smad5 mutant amnions isolated before visible malformations and tetraploid chimera analysis revealed two amnion defect sets. We attribute them to impairment of progenitors of the two main cell populations in amniotic ectoderm and to compromised cuboidal-to-squamous transition of anterior amniotic ectoderm. In both cases, SMAD5 is crucial for expanding amniotic ectoderm rapidly into a stretchable squamous sheet to accommodate exocoelom expansion, axial growth and folding morphogenesis. Summary: Clonal analysis shows that four distinct progenitor groups expand the normal amniotic ectoderm differently. In SMAD5-deficient mice, an undersized and abnormally nonsquamous amnion involves at least two impaired progenitor groups.
Alzheimers & Dementia | 2012
Bart Dermaut; Lies Vanden Broeck; Marina Naval Sanchez; Yoshitsugu Adachi; Danielle Diaper; Gernot Kleinberger; Marc Gistelinck; Christine Van Broeckhoven; Frank Hirth; Stein Aerts; Patrick Callaerts
CAUSED BYA FAILURE OF STEROID RECEPTOR–DEPENDENT TRANSCRIPTIONAL PROGRAM SWITCHING IN DROSOPHILA Bart Dermaut, Lies Vanden Broeck, Marina Naval Sanchez, Yoshitsugu Adachi, Danielle Diaper, Gernot Kleinberger, Marc Gistelinck, Christine Van Broeckhoven, Frank Hirth, Stein Aerts, Patrick Callaerts, Pasteur Institute of Lille, Lille, France; 2 VIB University of Leuven, Leuven, Belgium; 3 University of Leuven, Leuven, Belgium; 4 King’s College London, London, United Kingdom; University of Antwerp, Antwerpen, Belgium; King’s College London, London, Belgium.
Development | 2018
Mariya P. Dobreva; Vanesa Abon Escalona; Kirstie A. Lawson; Marina Naval Sanchez; Ljuba C. Ponomarev; Paulo N. G. Pereira; Agata Stryjewska; Nathan Criem; Danny Huylebroeck; Susana Lopes; Stein Aerts; An Zwijsen
Archive | 2013
Marina Naval Sanchez; Valerie Christiaens; Delphine Potier; Lotte Haagen; Stein Aerts
Archive | 2013
Delphine Potier; Kristofer Davie; Marina Naval Sanchez; Lotte Haagen; Van Han Huynh-Thu; Pierre Geurts; Duygu Koldere; Arzu Celik; Valerie Christiaens; Stein Aerts
Archive | 2012
Marina Naval Sanchez; Lotte Haagen; Valerie Christiaens; Bram Van de Sande; Stein Aerts