Alberto Martin | Fundacion Ciencia para la Vida (original) (raw)

Papers by Alberto Martin

Methods in Systems Biology, 2011

... Tianhai Tian 2.1 Introduction ... t " # ÀP d2vðtÞt ½ ð2.11Þ where u and v are molecular ... more ... Tianhai Tian 2.1 Introduction ... t " # ÀP d2vðtÞt ½ ð2.11Þ where u and v are molecular numbers of l CI and LacR, respectively, and s represents the effect of MMC on the degradation of l CI. Detailed information of the model parameters can be found in Tian and Burrage [67]. ...

Alteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerati... more Alteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene ...

MotivationThe regulation of gene expression is a key factor in the development and maintenance of... more MotivationThe regulation of gene expression is a key factor in the development and maintenance of life in all organisms. This process is carried out mainly through the action of transcription factors (TFs), although other actors such as ncRNAs are involved. In this work, we propose a new method to construct Gene Regulatory Networks (GRNs) depicting regulatory events in a certain context for Drosophila melanogaster. Our approach is based on known relationships between epigenetics and the activity of transcription factors.ResultsWe developed method, Tool for Weighted Epigenomic Networks in D. melanogaster (Fly T-WEoN), which generates GRNs starting from a reference network that contains all known gene regulations in the fly. Regulations that are unlikely taking place are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility...

Scientific Reports, 2019

Mathematical models based on Ordinary Differential Equations (ODEs) are frequently used to descri... more Mathematical models based on Ordinary Differential Equations (ODEs) are frequently used to describe and simulate biological systems. Nevertheless, such models are often difficult to understand. Unlike ODE models, Rule-Based Models (RBMs) utilise formal language to describe reactions as a cumulative number of statements that are easier to understand and correct. They are also gaining popularity because of their conciseness and simulation flexibility. However, RBMs generally lack tools to perform further analysis that requires simulation. This situation arises because exact and approximate simulations are computationally intensive. Translating RBMs into ODEs is commonly used to reduce simulation time, but this technique may be prohibitive due to combinatorial explosion. Here, we present the software calledPleioneto calibrate RBMs. Parameter calibration is essential given the incomplete experimental determination of reaction rates and the goal of using models to reproduce experimental ...

Journal of Bioinformatics and Computational Biology, 2008

Protein topology representations such as residue contact maps are an important intermediate step ... more Protein topology representations such as residue contact maps are an important intermediate step towards ab initio prediction of protein structure, but the problem of predicting reliable contact maps is far from solved. One of the main pitfalls of existing contact map predictors is that they generally predict unphysical maps, i.e. maps that cannot be embedded into three-dimensional structures or, at best, violate a number of basic constraints observed in real protein structures, such as the maximum number of contacts for a residue. Here, we focus on the problem of learning to predict more "physical" contact maps. We do so by first predicting contact maps through a traditional system (XXStout), and then filtering these maps by an ensemble of artificial neural networks. The filter is provided as input not only the bare predicted map, but also a number of global or long-range features extracted from it. In a rigorous cross-validation test, we show that the filter greatly impr...

Microorganisms, 2022

Clostridium baratii strains are rare opportunistic pathogens associated with botulism intoxicatio... more Clostridium baratii strains are rare opportunistic pathogens associated with botulism intoxication. They have been isolated from foods, soil and be carried asymptomatically or cause botulism outbreaks. Is not taxonomically related to Clostridium botulinum, but some strains are equipped with BoNT/F7 cluster. Despite their relationship with diseases, our knowledge regarding the genomic features and phylogenetic characteristics is limited. We analyzed the pangenome of C. baratii to understand the diversity and genomic features of this species. We compared existing genomes in public databases, metagenomes, and one newly sequenced strain isolated from an asymptomatic subject. The pangenome was open, indicating it comprises genetically diverse organisms. The core genome contained 28.49% of the total genes of the pangenome. Profiling virulence factors confirmed the presence of phospholipase C in some strains, a toxin capable of disrupting eukaryotic cell membranes. Furthermore, the genomic...

BMC bioinformatics, Jan 5, 2006

We describe Distill, a suite of servers for the prediction of protein structural features: second... more We describe Distill, a suite of servers for the prediction of protein structural features: secondary structure; relative solvent accessibility; contact density; backbone structural motifs; residue contact maps at 6, 8 and 12 Angstrom; coarse protein topology. The servers are based on large-scale ensembles of recursive neural networks and trained on large, up-to-date, non-redundant subsets of the Protein Data Bank. Together with structural feature predictions, Distill includes a server for prediction of Calpha traces for short proteins (up to 200 amino acids). The servers are state-of-the-art, with secondary structure predicted correctly for nearly 80% of residues (currently the top performance on EVA), 2-class solvent accessibility nearly 80% correct, and contact maps exceeding 50% precision on the top non-diagonal contacts. A preliminary implementation of the predictor of protein Calpha traces featured among the top 20 Novel Fold predictors at the last CASP6 experiment as group Dis...

We present a new knowledge-based Model Quality Assessment Program (MQAP) at the residue level whi... more We present a new knowledge-based Model Quality Assessment Program (MQAP) at the residue level which evaluates single protein structure models. We use a tree representation of the Cα trace to train a novel Neural Network Pairwise Interaction Field (NN-PIF) to predict the global quality of a model. We also attempt to extract local quality from global quality. The model allows fast evaluation of multiple differ-ent structure models for a single sequence. In our tests on a large set of structures, our model outperforms most other methods based on different and more complex protein structure representations in both local and global quality prediction. The method is available upon request from the authors. Method-specific rankers may also built by the authors upon request. 1

Increasingly large numbers of proteins require methods for functional annotation. This is typical... more Increasingly large numbers of proteins require methods for functional annotation. This is typically based on pairwise inference from the homology of either protein sequence or structure. Recently, similarity networks have been presented to leverage both the ability to visualize relationships between proteins and assess the transferability of functional inference. Here we present PANADA, a novel toolkit for the visualization and analysis of protein similarity networks in Cytoscape. Networks can be constructed based on pairwise sequence or structural alignments either on a set of proteins or, alternatively, by database search from a single sequence. The Panada web server, executable for download and examples

Fig. 2: Distribution of prediction accuracy as a function of sequence similarity to the best hit ... more Fig. 2: Distribution of prediction accuracy as a function of sequence similarity to the best hit in the templates (blue bars represent template-based predictions and red bars AI predictions). Fig. 5: The query interface for Porter+ predictions.

Motivation: Residue interaction networks (RINs) have been used in the literature to describe the ... more Motivation: Residue interaction networks (RINs) have been used in the literature to describe the protein 3D structure as a graph where nodes represent residues and edges physico–chemical interactions, e.g. hydrogen bonds or van-der-Waals contacts. Topological network parameters can be calculated over RINs and have been correlated with various aspects of protein structure and function. Here we present a novel web server, RING, to construct physico–chemically valid RINs interactively from PDB files for subsequent visualization in the Cytoscape platform. The additional structure-based parameters secondary structure, solvent accessibility and experimental uncertainty can be combined with information regarding residue conservation, mutual information and residue-based energy scoring functions. Different visualization styles are provided to facilitate visualization and standard plugins can be used to calculate topological parameters in Cytoscape. A sample use case analyzing the active sit...

ABSTRACTLeishmania spp. is the causal agent of several diseases called leishmaniases, neglected d... more ABSTRACTLeishmania spp. is the causal agent of several diseases called leishmaniases, neglected diseases that seek to be eradicated in the coming years. We aimed to study the genomic structure and function of non-coding RNAs (ncRNAs) from Leishmania spp. and to get insights into its RNAome. We studied 26 strains corresponding to 16 different species of Leishmania genus. RNAome analysis revealed the presence of several ncRNAs that are shared through different species, allowing us to differentiate between subgenus and as well as species that are canonically related to visceral leishmaniasis. We found coexpression relationships within coding genes and ncRNAs, thus suggesting possible functional relationships between different coding genes-ncRNAs. Expression analysis in the metacyclic developmental stage comparison for Leishmania braziliensis and Leishmania major reveals the presence of shared coexpressed ncRNAs to several other coding genes in both species involved in chromatin structu...

Microbiology Spectrum

This work opens a new path to fight parasites by targeting host molecular functions by repurposin... more This work opens a new path to fight parasites by targeting host molecular functions by repurposing available and approved drugs. We created a novel approach to identify key proteins involved in any biological process by combining gene regulatory networks and expression profiles.

Motivation: Residue interaction networks (RINs) have been used in the literature to describe the ... more Motivation: Residue interaction networks (RINs) have been used in the literature to describe the protein three-dimensional structure as a graph where nodes represent residues and edges physico-chemical interactions, e.g. hydrogen bonds or van-der-Waals contacts. Topo-logical network parameters can be calculated over RINs and have been correlated with various aspects of protein structure and func-tion. Here we present a novel web server, RING, to construct phys-ico-chemically valid RINs interactively from PDB files for subsequent visualization in the Cytoscape platform. The additional structure-based parameters secondary structure, solvent accessibility and experimental uncertainty can be combined with information regard-ing residue conservation, mutual information and residue-based energy scoring functions. Different visualization styles are provided to facilitate visualization and standard plugins can be used to calcu-late topological parameters in Cytoscape. A sample use case ana-...

PeerJ

Protein structure is not static; residues undergo conformational rearrangements and, in doing so,... more Protein structure is not static; residues undergo conformational rearrangements and, in doing so, create, stabilize or break non-covalent interactions. Molecular dynamics (MD) is a technique used to simulate these movements with atomic resolution. However, given the data-intensive nature of the technique, gathering relevant information from MD simulations is a complex and time consuming process requiring several computational tools to perform these analyses. Among different approaches, the study of residue interaction networks (RINs) has proven to facilitate the study of protein structures. In a RIN, nodes represent amino-acid residues and the connections between them depict non-covalent interactions. Here, we describe residue interaction networks in protein molecular dynamics (RIP-MD), a visual molecular dynamics (VMD) plugin to facilitate the study of RINs using trajectories obtained from MD simulations of proteins. Our software generates RINs from MD trajectory files. The non-cov...

Frontiers in Molecular Biosciences

Methods in molecular biology (Clifton, N.J.), 2018

Complex systems are governed by dynamic processes whose underlying causal rules are difficult to ... more Complex systems are governed by dynamic processes whose underlying causal rules are difficult to unravel. However, chemical reactions, molecular interactions, and many other complex systems can be usually represented as concentrations or quantities that vary over time, which provides a framework to study these dynamic relationships. An increasing number of tools use these quantifications to simulate dynamically complex systems to better understand their underlying processes. The application of such methods covers several research areas from biology and chemistry to ecology and even social sciences.In the following chapter, we introduce the concept of rule-based simulations based on the Stochastic Simulation Algorithm (SSA) as well as other mathematical methods such as Ordinary Differential Equations (ODE) models to describe agent-based systems. Besides, we describe the mathematical framework behind Kappa (κ), a rule-based language for the modeling of complex systems, and some extens...

BMC genomics, Jan 5, 2018

The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, in... more The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD. We used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryo...

Methods in Systems Biology, 2011

... Tianhai Tian 2.1 Introduction ... t " # ÀP d2vðtÞt ½ ð2.11Þ where u and v are molecular ... more ... Tianhai Tian 2.1 Introduction ... t " # ÀP d2vðtÞt ½ ð2.11Þ where u and v are molecular numbers of l CI and LacR, respectively, and s represents the effect of MMC on the degradation of l CI. Detailed information of the model parameters can be found in Tian and Burrage [67]. ...

Alteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerati... more Alteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene ...

MotivationThe regulation of gene expression is a key factor in the development and maintenance of... more MotivationThe regulation of gene expression is a key factor in the development and maintenance of life in all organisms. This process is carried out mainly through the action of transcription factors (TFs), although other actors such as ncRNAs are involved. In this work, we propose a new method to construct Gene Regulatory Networks (GRNs) depicting regulatory events in a certain context for Drosophila melanogaster. Our approach is based on known relationships between epigenetics and the activity of transcription factors.ResultsWe developed method, Tool for Weighted Epigenomic Networks in D. melanogaster (Fly T-WEoN), which generates GRNs starting from a reference network that contains all known gene regulations in the fly. Regulations that are unlikely taking place are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility...

Scientific Reports, 2019

Mathematical models based on Ordinary Differential Equations (ODEs) are frequently used to descri... more Mathematical models based on Ordinary Differential Equations (ODEs) are frequently used to describe and simulate biological systems. Nevertheless, such models are often difficult to understand. Unlike ODE models, Rule-Based Models (RBMs) utilise formal language to describe reactions as a cumulative number of statements that are easier to understand and correct. They are also gaining popularity because of their conciseness and simulation flexibility. However, RBMs generally lack tools to perform further analysis that requires simulation. This situation arises because exact and approximate simulations are computationally intensive. Translating RBMs into ODEs is commonly used to reduce simulation time, but this technique may be prohibitive due to combinatorial explosion. Here, we present the software calledPleioneto calibrate RBMs. Parameter calibration is essential given the incomplete experimental determination of reaction rates and the goal of using models to reproduce experimental ...

Journal of Bioinformatics and Computational Biology, 2008

Protein topology representations such as residue contact maps are an important intermediate step ... more Protein topology representations such as residue contact maps are an important intermediate step towards ab initio prediction of protein structure, but the problem of predicting reliable contact maps is far from solved. One of the main pitfalls of existing contact map predictors is that they generally predict unphysical maps, i.e. maps that cannot be embedded into three-dimensional structures or, at best, violate a number of basic constraints observed in real protein structures, such as the maximum number of contacts for a residue. Here, we focus on the problem of learning to predict more "physical" contact maps. We do so by first predicting contact maps through a traditional system (XXStout), and then filtering these maps by an ensemble of artificial neural networks. The filter is provided as input not only the bare predicted map, but also a number of global or long-range features extracted from it. In a rigorous cross-validation test, we show that the filter greatly impr...

Microorganisms, 2022

Clostridium baratii strains are rare opportunistic pathogens associated with botulism intoxicatio... more Clostridium baratii strains are rare opportunistic pathogens associated with botulism intoxication. They have been isolated from foods, soil and be carried asymptomatically or cause botulism outbreaks. Is not taxonomically related to Clostridium botulinum, but some strains are equipped with BoNT/F7 cluster. Despite their relationship with diseases, our knowledge regarding the genomic features and phylogenetic characteristics is limited. We analyzed the pangenome of C. baratii to understand the diversity and genomic features of this species. We compared existing genomes in public databases, metagenomes, and one newly sequenced strain isolated from an asymptomatic subject. The pangenome was open, indicating it comprises genetically diverse organisms. The core genome contained 28.49% of the total genes of the pangenome. Profiling virulence factors confirmed the presence of phospholipase C in some strains, a toxin capable of disrupting eukaryotic cell membranes. Furthermore, the genomic...

BMC bioinformatics, Jan 5, 2006

We describe Distill, a suite of servers for the prediction of protein structural features: second... more We describe Distill, a suite of servers for the prediction of protein structural features: secondary structure; relative solvent accessibility; contact density; backbone structural motifs; residue contact maps at 6, 8 and 12 Angstrom; coarse protein topology. The servers are based on large-scale ensembles of recursive neural networks and trained on large, up-to-date, non-redundant subsets of the Protein Data Bank. Together with structural feature predictions, Distill includes a server for prediction of Calpha traces for short proteins (up to 200 amino acids). The servers are state-of-the-art, with secondary structure predicted correctly for nearly 80% of residues (currently the top performance on EVA), 2-class solvent accessibility nearly 80% correct, and contact maps exceeding 50% precision on the top non-diagonal contacts. A preliminary implementation of the predictor of protein Calpha traces featured among the top 20 Novel Fold predictors at the last CASP6 experiment as group Dis...

We present a new knowledge-based Model Quality Assessment Program (MQAP) at the residue level whi... more We present a new knowledge-based Model Quality Assessment Program (MQAP) at the residue level which evaluates single protein structure models. We use a tree representation of the Cα trace to train a novel Neural Network Pairwise Interaction Field (NN-PIF) to predict the global quality of a model. We also attempt to extract local quality from global quality. The model allows fast evaluation of multiple differ-ent structure models for a single sequence. In our tests on a large set of structures, our model outperforms most other methods based on different and more complex protein structure representations in both local and global quality prediction. The method is available upon request from the authors. Method-specific rankers may also built by the authors upon request. 1

Increasingly large numbers of proteins require methods for functional annotation. This is typical... more Increasingly large numbers of proteins require methods for functional annotation. This is typically based on pairwise inference from the homology of either protein sequence or structure. Recently, similarity networks have been presented to leverage both the ability to visualize relationships between proteins and assess the transferability of functional inference. Here we present PANADA, a novel toolkit for the visualization and analysis of protein similarity networks in Cytoscape. Networks can be constructed based on pairwise sequence or structural alignments either on a set of proteins or, alternatively, by database search from a single sequence. The Panada web server, executable for download and examples

Fig. 2: Distribution of prediction accuracy as a function of sequence similarity to the best hit ... more Fig. 2: Distribution of prediction accuracy as a function of sequence similarity to the best hit in the templates (blue bars represent template-based predictions and red bars AI predictions). Fig. 5: The query interface for Porter+ predictions.

Motivation: Residue interaction networks (RINs) have been used in the literature to describe the ... more Motivation: Residue interaction networks (RINs) have been used in the literature to describe the protein 3D structure as a graph where nodes represent residues and edges physico–chemical interactions, e.g. hydrogen bonds or van-der-Waals contacts. Topological network parameters can be calculated over RINs and have been correlated with various aspects of protein structure and function. Here we present a novel web server, RING, to construct physico–chemically valid RINs interactively from PDB files for subsequent visualization in the Cytoscape platform. The additional structure-based parameters secondary structure, solvent accessibility and experimental uncertainty can be combined with information regarding residue conservation, mutual information and residue-based energy scoring functions. Different visualization styles are provided to facilitate visualization and standard plugins can be used to calculate topological parameters in Cytoscape. A sample use case analyzing the active sit...

ABSTRACTLeishmania spp. is the causal agent of several diseases called leishmaniases, neglected d... more ABSTRACTLeishmania spp. is the causal agent of several diseases called leishmaniases, neglected diseases that seek to be eradicated in the coming years. We aimed to study the genomic structure and function of non-coding RNAs (ncRNAs) from Leishmania spp. and to get insights into its RNAome. We studied 26 strains corresponding to 16 different species of Leishmania genus. RNAome analysis revealed the presence of several ncRNAs that are shared through different species, allowing us to differentiate between subgenus and as well as species that are canonically related to visceral leishmaniasis. We found coexpression relationships within coding genes and ncRNAs, thus suggesting possible functional relationships between different coding genes-ncRNAs. Expression analysis in the metacyclic developmental stage comparison for Leishmania braziliensis and Leishmania major reveals the presence of shared coexpressed ncRNAs to several other coding genes in both species involved in chromatin structu...

Microbiology Spectrum

This work opens a new path to fight parasites by targeting host molecular functions by repurposin... more This work opens a new path to fight parasites by targeting host molecular functions by repurposing available and approved drugs. We created a novel approach to identify key proteins involved in any biological process by combining gene regulatory networks and expression profiles.

Motivation: Residue interaction networks (RINs) have been used in the literature to describe the ... more Motivation: Residue interaction networks (RINs) have been used in the literature to describe the protein three-dimensional structure as a graph where nodes represent residues and edges physico-chemical interactions, e.g. hydrogen bonds or van-der-Waals contacts. Topo-logical network parameters can be calculated over RINs and have been correlated with various aspects of protein structure and func-tion. Here we present a novel web server, RING, to construct phys-ico-chemically valid RINs interactively from PDB files for subsequent visualization in the Cytoscape platform. The additional structure-based parameters secondary structure, solvent accessibility and experimental uncertainty can be combined with information regard-ing residue conservation, mutual information and residue-based energy scoring functions. Different visualization styles are provided to facilitate visualization and standard plugins can be used to calcu-late topological parameters in Cytoscape. A sample use case ana-...

PeerJ

Protein structure is not static; residues undergo conformational rearrangements and, in doing so,... more Protein structure is not static; residues undergo conformational rearrangements and, in doing so, create, stabilize or break non-covalent interactions. Molecular dynamics (MD) is a technique used to simulate these movements with atomic resolution. However, given the data-intensive nature of the technique, gathering relevant information from MD simulations is a complex and time consuming process requiring several computational tools to perform these analyses. Among different approaches, the study of residue interaction networks (RINs) has proven to facilitate the study of protein structures. In a RIN, nodes represent amino-acid residues and the connections between them depict non-covalent interactions. Here, we describe residue interaction networks in protein molecular dynamics (RIP-MD), a visual molecular dynamics (VMD) plugin to facilitate the study of RINs using trajectories obtained from MD simulations of proteins. Our software generates RINs from MD trajectory files. The non-cov...

Frontiers in Molecular Biosciences

Methods in molecular biology (Clifton, N.J.), 2018

Complex systems are governed by dynamic processes whose underlying causal rules are difficult to ... more Complex systems are governed by dynamic processes whose underlying causal rules are difficult to unravel. However, chemical reactions, molecular interactions, and many other complex systems can be usually represented as concentrations or quantities that vary over time, which provides a framework to study these dynamic relationships. An increasing number of tools use these quantifications to simulate dynamically complex systems to better understand their underlying processes. The application of such methods covers several research areas from biology and chemistry to ecology and even social sciences.In the following chapter, we introduce the concept of rule-based simulations based on the Stochastic Simulation Algorithm (SSA) as well as other mathematical methods such as Ordinary Differential Equations (ODE) models to describe agent-based systems. Besides, we describe the mathematical framework behind Kappa (κ), a rule-based language for the modeling of complex systems, and some extens...

BMC genomics, Jan 5, 2018

The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, in... more The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD. We used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryo...