Marta R. Hidalgo

Centro de Investigación Príncipe Felipe | CIPF · Systems Genomics

Background Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Previous studies have suggested that the dopamine D2 receptor gene and genes involved in glutamatergic neurotransmission, synaptic plasticity, and...

Background: As the housekeeping genes (HKG) generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal controls in gene expression studies. Nevertheless, HKG may vary gene expression profile according to different variables introduc...

Highlights Females show a significant increase in the expression of MED31 in the frontal cortex. This gene is involved in lipid metabolism and neural diseases. We found 237 genes having sex-based significantly differential expression in substantia nigra. Functional profiling of these genes reveals a differential sex-related behavior in PD regarding...

Epigenetic changes are involved in the onset and progression of cancer, and the detection of DNA methylation signatures may foster the improvement of diagnosis and prognosis. While the emergence of innovative technologies has fostered numerous studies in breast cancer, many lack statistical power due to the small sample sizes generally involved. In...

Minimal hepatic encephalopathy (MHE) is diagnosed using PHES battery, but other tests are more sensitive, and a simple tool for early MHE detection is required. Assessment of saccadic eye movements is useful for early detection of cognitive alterations in different pathologies. We characterized the alterations in saccadic eye movements in MHE patie...

Background:In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson's disease incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in Parkinson’s Disease as epidemiological and clinical features differ between males and females. Methods: To s...

Background: Multiple sclerosis (MS), a chronic auto-immune, inflammatory, and degenerative disease of the central nervous system, affects both males and females; however, females suffer from a higher risk of developing MS (2-3:1 ratio relative to males). The precise sex-based factors influencing risk of MS are currently unknown. Here, we explore th...

Neural progenitor cell (NPC) transplantation represents a promising treatment strategy for spinal cord injury (SCI); however, the underlying therapeutic mechanisms remain incompletely understood. We demonstrate that severe spinal contusion in adult rats causes transcriptional dysregulation, which persists from early subacute to chronic stages of SC...

Background: As the housekeeping genes generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal controls in gene expression studies. Nevertheless, multiple studies indicate that not all housekeeping genes display stable expression...

Housekeeping genes (HKG), those involved in the maintenance of basic cell functions, are considered to have constant expression levels in all cell types, and are therefore commonly used as internal controls in gene expression studies. Nevertheless, multiple studies have shown that not all of them have stable expression levels across different cells...

Background Previous studies have described sex-based differences in the epidemiological and clinical patterns of non-alcoholic fatty liver disease (NAFLD); however, we understand relatively little regarding the underlying molecular mechanisms. Herein, we present the first systematic review and meta-analysis of NAFLD transcriptomic studies to identi...

In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson’s disease (PD) incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in PD as epidemiological and clinical features differ between males and females. To study sex bias in PD, we conducte...

Background Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory, and degenerative disease of the central nervous system that affects both women and men but the risk of developing MS is higher in women (2-3:1 ratio compared to men). Current knowledge does not allow a precise definition of the sex-related factors intervening in MS. Here, we...

Sex and gender differences in different health scenarios has been thoroughly acknowledged in the literature, and yet, very scarcely analyzed. To fill the gap, here we present MetaFun, which allows to meta-analyze multiple omics datasets with a sex-based perspective, and to combine different datasets to gain major statistical power and to assist the...

Background Cancer is a major health problem which presents a high heterogeneity. In this work we explore omics data from Breast, Kidney and Lung cancers at different levels as signalling pathways, functions and miRNAs, as part of the CAMDA 2019 Hi-Res Cancer Data Integration Challenge. Our goal is to find common functional patterns which give rise...

Genome-scale mechanistic models of pathways are gaining importance for genomic data interpretation because they provide a natural link between genotype measurements (transcriptomics or genomics data) and the phenotype of the cell (its functional behavior). Moreover, mechanistic models can be used to predict the potential effect of interventions, in...

Here 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 inf...

In the last decade, different omic technologies have experiences an exponential technological advancement. However, metabolomics has not followed a similarly vertiginous improving improvement and are far from genomics or transcriptomics in terms of throughput, cost and even accuracy. Therefore, genome-scale in-silico methodologies to estimate metab...

While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic dat...

The abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder (AUD). An impaired ability to stop or control alcohol intake despite adverse health or social consequences characterize AUD. While AUDs predominantly occur in men, growing evidence sugg...

While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic dat...

The abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder (AUD). An impaired ability to stop or control alcohol intake despite adverse health or social consequences characterize AUD. While AUDs predominantly occur in men, growing evidence sugg...

Here 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 inf...

Here 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 inf...

Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteo...

Background & aims Sex differences in non-alcoholic fatty liver disease (NAFLD) are well known and yet, most of the studies available in the literature do not include this factor when analysing the data. Here we present a functional meta-analysis of NAFLD studies to detect the molecular mechanisms involved in its progression, distinguishing any diff...

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...

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,...

Background : Cancer is an extremely heterogeneous disease, both intra and inter cancer types. In this work we aim to establish common patterns in Breast, Kidney and Lung cancers at the signaling pathways and functional level which give rise to the generic microenvironment of cancer, as well as determine cancer-specific pathways and functions relate...

The sustained generation of genomic data in the last decade has increased the knowledge on the causal mutations of a large number of diseases, especially for highly penetrant Mendelian diseases, typically caused by a unique or a few genes. However, the discovery of causal genes in complex diseases has been far less successful. Many complex diseases...

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 d...

In spite of the increasing availability of genomic and transcriptomic data, there is still a gap between the detection of perturbations in gene expression and the understanding of their contribution to the molecular mechanisms that ultimately account for the phenotype studied. Alterations in the metabolism are behind the initiation and progression...

Lung cancer is the most common cause of cancer death worldwide, and 85% of patients belongs to a subtype known as non small cell lung cancer. Although it is greatly associated with smoking, lung cancer in never smokers is more common in women than men. Understanding its biology and molecular mechanisms is crucial for the development of effective th...

Non-alcoholic fatty liver disease (NAFLD) is one of the most important illnesses that can lead to advanced liver disease, cirrhosis and hepatocellular carcinoma (HCC). The prevalence of NAFLD has increased dramatically in recent years and is estimated at 24% throughout the world. As also occurs in other diseases (such as lung cancer or some autoimm...

Non-alcoholic fatty liver disease (NAFLD) is one of the most important illnesses that can lead to advanced liver disease, cirrhosis and hepatocellular carcinoma (HCC). The prevalence of NAFLD has increased dramatically in recent years and is estimated at 24% throughout the world. As also occurs in other diseases (such as lung cancer or some autoimm...

Clinical and epidemiological indicators show a large number of diseases and health scenarios where gender differences are detected but the underlying causes of these changes are still unknown. The detection of these biological, clinical and psychosocial causes would allow us to be more precise in the diagnosis and in the personalized selection of t...

Background: Despite the progress in neuroblastoma therapies the mortality of high-risk patients is still high (40-50%) and the molecular basis of the disease remains poorly known. Recently, a mathematical model was used to demonstrate that the network regulating stress signaling by the c-Jun N-terminal kinase pathway played a crucial role in survi...

Metabolic reprogramming plays an important role in cancer development and progression and is a well-established hallmark of cancer. Despite its inherent complexity, cellular metabolism can be decomposed into functional modules that represent fundamental metabolic processes. Here, we performed a pan-cancer study involving 9,428 samples from 25 cance...

In spite of the increasing availability of genomic and transcriptomic data, there is still a gap between the detection of perturbations in gene expression and the understanding of their contribution to the molecular mechanisms that ultimately account for the phenotype studied. Alterations in the metabolism are behind the initiation and progression...

Understanding the aspects of cell functionality that account for disease mechanisms or drug modes of action is a main challenge for precision medicine. Classical gene-based approaches ignore the modular nature of most human traits, whereas conventional pathway enrichment approaches produce only illustrative results of limited practical utility. Rec...

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from...

Motivation: Current plant and animal genomic studies are often based on newly assembled genomes that have not been properly consolidated. In this scenario, misassembled regions can easily lead to false positive findings. Despite quality control scores are included within genotyping protocols, they are usually employed to evaluate individual sample...

With the advent of high-throughput technologies for genome-wide expression profiling, a large number of methods have been proposed to discover gene-based signatures as biomarkers to guide cancer prognosis. However, it is often difficult to interpret the list of genes in a prognostic signature regarding the underlying biological processes responsibl...

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measu...

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measu...

The discovery of actionable targets is crucial for targeted therapies and is also a constituent part of the drug discovery process. The success of an intervention over a target depends critically on its contribution, within the complex network of gene interactions, to the cellular processes responsible for disease progression or therapeutic respons...

In this work we describe an algorithm to generate tree-decomposable minimally rigid graphs on a given set of vertices V. The main idea is based on the well-known fact that all minimally rigid graphs, also known as Laman graphs, can be generated via Henneberg sequences. Given that not each minimally rigid graph is tree-decomposable, we identify a se...