Paintomics: a web based tool for the joint visualization of transcriptomics and metabolomics data

Motivation: The development of the omics technologies such as transcriptomics, proteomics and metabolomics has made possible the realization of systems biology studies where biological systems are interrogated at different levels of biochemical activity (gene expression, protein activity and/or metabolite concentration). An effective approach to the analysis of these complex datasets is the joined visualization of the disparate biomolecular data on the framework of known biological pathways

Computational modelling of epithelial cell monolayers during infection with Listeria monocytogenes

Intracellular bacterial infections alter the normal functionality of human host cells and tissues. Infection can also modify the mechanical properties of host cells, altering the mechanical equilibrium of tissues. In order to advance our understanding of host–pathogen interactions, simplified in vitro models are normally used. However, in vitro studies present certain limitations that can be alleviated by the use of computer-based models. As complementary tools these computational models, in conjunction with in vitro experiments, can enhance our understanding of the mechanisms of action underlying infection processes. In this work, we extend our previous computer-based model to simulate infection of epithelial cells with the intracellular bacterial pathogen Listeria monocytogenes. We found that forces generated by host cells play a regulatory role in the mechanobiological response to infection. After infection, in silico cells alter their mechanical properties in order to achieve a new mechanical equilibrium. The model pointed the key role of cell–cell and cell–extracellular matrix interactions in the mechanical competition of bacterial infection. The obtained results provide a more detailed description of cell and tissue responses to infection, and could help inform future studies focused on controlling bacterial dissemination and the outcome of infection processes. © 2022 The Author(s

An intuitionistic approach to scoring DNA sequences against transcription factor binding site motifs

Background: Transcription factors (TFs) control transcription by binding to specific regions of DNA called transcription factor binding sites (TFBSs). The identification of TFBSs is a crucial problem in computational biology and includes the subtask of predicting the location of known TFBS motifs in a given DNA sequence. It has previously been shown that, when scoring matches to known TFBS motifs, interdependencies between positions within a motif should be taken into account. However, this remains a challenging task owing to the fact that sequences similar to those of known TFBSs can occur by chance with a relatively high frequency. Here we present a new method for matching sequences to TFBS motifs based on intuitionistic fuzzy sets (IFS) theory, an approach that has been shown to be particularly appropriate for tackling problems that embody a high degree of uncertainty. Results: We propose SCintuit, a new scoring method for measuring sequence-motif affinity based on IFS theory. Unlike existing methods that consider dependencies between positions, SCintuit is designed to prevent overestimation of less conserved positions of TFBSs. For a given pair of bases, SCintuit is computed not only as a function of their combined probability of occurrence, but also taking into account the individual importance of each single base at its corresponding position. We used SCintuit to identify known TFBSs in DNA sequences. Our method provides excellent results when dealing with both synthetic and real data, outperforming the sensitivity and the specificity of two existing methods in all the experiments we performed. Conclusions: The results show that SCintuit improves the prediction quality for TFs of the existing approaches without compromising sensitivity. In addition, we show how SCintuit can be successfully applied to real research problems. In this study the reliability of the IFS theory for motif discovery tasks is proven

Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 +/- 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3-3.1), CRC (HR 4.4, 95% CI 1.1-17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0-2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3-5.8), rectal bleeding (OR 0.3, 95% CI 0.1-0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7-7.1). However, CEA was increased only in 31.8% (95% CI, 16.4-52.7%) and 50% (95% CI, 25.4-74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Evolución paleoambiental de la mitad sur de la Península Ibérica. Aplicación a la evaluación del comportamiento de los repositorios de residuos radiactivos

Esta publicación refleja los resultados obtenidos de la realización de los proyectos "EQUIP: Evidency from Quaternary Infills Palaeohydrogeology" (F 14W/ CT96/0031), financiado por la UE, "Evolución Paleoclimática de [a Mitad Sur de [a Península Ibérica" financiado por ENRESA y "Paleoclima" financiado por el Consejo de Seguridad Nuclear y ENRESA. La cuenca de Guadix-Baza, sector oriental, es una de las escasas zonas europeas donde se ha conservado un registro razonablemente completo del Pleistoceno. La cuenca de Guadix Baza, en régimen continental desde el Plioceno, funcionó bajo un régimen centrípeto, con abanicos aluviales en los bordes y una zona compleja lacustre en mosaico en su centro. Se ha podido establecer la existencia de una amplia variedad de facies aluviales y fluviales y sus interrelaciones. La sedimentación en el margen lacustre estaba constituida por arenas bioclásticas y lutitas con fósiles, mientras que en zonas más centrales predominaron lutitas yesíferas, lutitas con yeso intrasedimentario, arenas yesíferas yesos y, ocasionalmente, carbonatos que durante un período concreto depositaron los materiales que configuran el "Nivel Calcáreo de Orce", calizas y dolomías con cantidades variables de yeso y terrígenos cerca de los bordes. El trabajo de campo permitió el establecimiento de una serie estratigráfica tipo compuesta, que refleja los principales acontecimiento paleoambientales que tuvieron lugar durante el Pleistoceno. Con el fin de evitar la yesificación de la calcita y aragonito, propia del ambiente lacustre, la serie tipo de ha establecido en el registro del margen lacustre. Con ayuda del análisis paleomagnético y el análisis de la racemización de aminoácidos en conchas de moluscos y ostrácodos se ha establecido la cronología numérica de la sección estratigráfica tipo que cubre desde el límite Plioceno-Pleistoceno hasta unos 250 ka BP, cuando la erosión de la cabecera del río Fardes alcanza la cuenca abriéndola hacia el valle del Guadalquivir y cesando [a sedimentación lacustre. También se ha datado un depósito de terraza fluvial. Se han obtenido datos paleoambientales "instantáneos" mediante el estudio palinológico, el análisis paleobotánico de material silicificado (madera opalizada) o carbonizado (análisis paleoantracológico), el análisis geoquímico orgánico de algunos niveles especialmente favorables. La geoquímica orgánica de biomarcadores de algunos niveles concretos proporcionó datos sobre su origen (plantas terrestres o acuáticas) y confirmó que un conspicuo nivel carbonoso tuvo su origen en un incendio forestal. El análisis paleobiológico basado en la distribución de especies de ostrácodos, gasterópodos y pelecípodos ha permitido una primera aproximación paleoambiental, pese al evidente sesgo introducido por la presencia de fuentes salinas y materiales yesíferos en el área fuente de los abanicos aluviales del límite oriental de la cuenca. Esta interpretación se ha depurado mediante el estudio geoquímico inorgánico, isótopos estables y elementos traza de las conchas calcíticas de ostrácodos. Ello ha permitido el establecimiento de una alternancia de períodos "fríos y húmedos" y "cálidos y áridos" que permiten reconocer de las clases climáticas "mediterráneo seco" y "mediterráneo húmedo" sensu Horowitz (1989), que tienen sus correlatos en el registro paleoclimático de los grandes lagos del rift del Mar Muerto, el Mar Caspio y lagos pluviales de Norte América. La correlación de los datos isotópicos con las paleosalinidades deducidas del estudio de las inclusiones fluidas en yeso intrasedimentario ha permitido corroborar estas interpretaciones. Esto plantea un nuevo enfoque en el análisis del comportamiento de los repositorios de residuos radiactivos de alta

Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases

Machine-learning based patient classification using Hepatitis B virus full-length genome quasispecies from Asian and European cohorts

Chronic infection with Hepatitis B virus (HBV) is a major risk factor for the development of advanced liver disease including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The relative contribution of virological factors to disease progression has not been fully defined and tools aiding the deconvolution of complex patient virus profiles is an unmet clinical need. Vari

Retrospective cohort study: Risk of gastrointestinal cancer in a symptomatic cohort after a complete colonoscopy: Role of faecal immunochemical test

BACKGROUND: Faecal immunochemical test (FIT) has been recommended to assess symptomatic patients for colorectal cancer (CRC) detection. Nevertheless, some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized. A positive FIT result could be related to other gastrointestinal cancers (GIC). AIM: To assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 µg Hb/g faeces) without CRC. METHODS: Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection. Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare, underwent a quantitative FIT before undergoing a complete colonoscopy. Patients without CRC were divided into two groups (positive and negative FIT) using the threshold of 10 µg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate (HR) was calculated adjusted by age, sex and presence of significant colonic lesion. RESULTS: We included 2709 patients without CRC and a complete baseline colonoscopy, 730 (26.9%) with FIT = 10 µgr Hb/gr. During a mean time of 45.5 ± 20.0 mo, a GIC was detected in 57 (2.1%) patients: An upper GIC in 35 (1.3%) and a CRC in 14 (0.5%). Thirty-six patients (1.3%) died due to GIC: 22 (0.8%) due to an upper GIC and 9 (0.3%) due to CRC. FIT-positive subjects showed a higher CRC risk (HR 3.8, 95%CI: 1.2-11.9) with no differences in GIC (HR 1.5, 95%CI: 0.8-2.7) or upper GIC risk (HR 1.0, 95%CI: 0.5-2.2). Patients with a positive FIT had only an increased risk of CRC-related death (HR 10.8, 95%CI: 2.1-57.1) and GIC-related death (HR 2.2, 95%CI: 1.1-4.3), with no differences in upper GIC-related death (HR 1.4, 95%CI: 0.6-3.3). An upper GIC was detected in 22 (0.8%) patients during the first year. Two variables were independently associated: anaemia (OR 5.6, 95%CI: 2.2-13.9) and age = 70 years (OR 2.7, 95%CI: 1.1-7.0). CONCLUSION: Symptomatic patients without CRC have a moderate risk increase in upper GIC, regardless of the FIT result. Patients with a positive FIT have an increased risk of post-colonoscopy CRC