STATegra: Multi-Omics Data Integration - A Conceptual Scheme With a Bioinformatics Pipeline

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining available multi-omic anlaysis tools (machine learning component analysis, non-parametric data combination, and a multi-omics exploratory analysis) in a step-wise manner. While in several studies, we have previously combined those integrative tools, here, we provide a systematic description of the STATegra framework and its validation using two The Cancer Genome Atlas (TCGA) case studies. For both, the Glioblastoma and the Skin Cutaneous Melanoma (SKCM) cases, we demonstrate an enhanced capacity of the framework (and beyond the individual tools) to identify features and pathways compared to single-omics analysis. Such an integrative multi-omics analysis framework for identifying features and components facilitates the discovery of new biology. Finally, we provide several options for applying the STATegra framework when parametric assumptions are fulfilled and for the case when not all the samples are profiled for all omics. The STATegra framework is built using several tools, which are being integrated step-by-step as OpenSource in the STATegRa Bioconductor packag

Análisis de datos de estudios epidemiológicos con datos faltantes: métodos y aplicación en el estudio Universidad y Salud Mental (Estudio UniverSal)

La presencia de los datos faltantes es un problema metodológico común de la investigación en salud. En este trabajo se han introducido los métodos imputación múltiple (MI) y ponderación por la probabilidad inversa (IPW) para tratar los datos faltantes y se han aplicado en el estudio UniverSal, un estudio multicéntrico y longitudinal que recoge información autorreportada de estudiantes universitarios sobre ideación y conducta suicida y los posibles factores de riesgo y protección. Se han estimado prevalencias de diferentes variables estudiadas y se ha aplicado un modelo de regresión Poisson de los posibles factores de riesgo y protección asociados con tener pensamiento o conducta suicida con el objetivo de comparar los resultados obtenidos al aplicar MI e IPW

Análisis de datos de estudios epidemiológicos con datos faltantes: métodos y aplicación en el estudio Universidad y Salud Mental (Estudio UniverSal)

La presencia de los datos faltantes es un problema metodológico común de la investigación en salud. En este trabajo se han introducido los métodos imputación múltiple (MI) y ponderación por la probabilidad inversa (IPW) para tratar los datos faltantes y se han aplicado en el estudio UniverSal, un estudio multicéntrico y longitudinal que recoge información autorreportada de estudiantes universitarios sobre ideación y conducta suicida y los posibles factores de riesgo y protección. Se han estimado prevalencias de diferentes variables estudiadas y se ha aplicado un modelo de regresión Poisson de los posibles factores de riesgo y protección asociados con tener pensamiento o conducta suicida con el objetivo de comparar los resultados obtenidos al aplicar MI e IPW

Análisis de datos de estudios epidemiológicos con datos faltantes: métodos y aplicación en el estudio Universidad y Salud Mental (Estudio UniverSal)

La presencia de los datos faltantes es un problema metodológico común de la investigación en salud. En este trabajo se han introducido los métodos imputación múltiple (MI) y ponderación por la probabilidad inversa (IPW) para tratar los datos faltantes y se han aplicado en el estudio UniverSal, un estudio multicéntrico y longitudinal que recoge información autorreportada de estudiantes universitarios sobre ideación y conducta suicida y los posibles factores de riesgo y protección. Se han estimado prevalencias de diferentes variables estudiadas y se ha aplicado un modelo de regresión Poisson de los posibles factores de riesgo y protección asociados con tener pensamiento o conducta suicida con el objetivo de comparar los resultados obtenidos al aplicar MI e IPW

Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis

Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acutely decompensated cirrhosis, and is characterized by intense systemic inflammation, multi-organ failure and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules generated from polyunsaturated fatty acids released from membrane phospholipids that play a major role in inflammation and immunity, is poorly characterized in ACLF. In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acutely decompensated cirrhosis, with (n=119) and without (n=127) ACLF, and from healthy subjects (HS, n=18). Measurements were prospectively repeated in 191 patients with acutely decompensated cirrhosis during a 28-day follow-up period. Fifty-nine lipid mediators (out of 100) were detected in plasma from cirrhotic patients, of which, 16 were significantly associated with the disease status. Among these, 11 lipid mediators distinguished patients at any stage from HS, whereas two lipid mediators (leukotriene [LT] E4 and 12-hydroxyheptadecatrienoic acid, both derived from arachidonic acid) shaped a minimal plasma fingerprint that discriminated patients with ACLF from those without. Levels of LTE4 distinguished ACLF grade 3 from ACLF grades 1 and 2, followed the clinical course of the disease (increased with worsening and decreased with improvement) and positively correlated with markers of inflammation and non-apoptotic cell death. Moreover, LTE4 together with LXA5 (derived from eicosapentaenoic acid) and EKODE (derived from linoleic acid) associated with short-term mortality. Interestingly, LXA5 and EKODE formed a signature profile associated with coagulation and liver failures. Taken together, these findings uncover specific lipid mediator profiles associated with severity and prognosis of patients with acutely decompensated cirrhosis

First-onset and persistence of suicidal ideation in university students: A one-year follow-up study

Background: Longitudinal evidence about risk and protective factors for suicidal ideation among university students is limited. Methods: 12-month first-onset and persistence of suicidal ideation (SI) among Spanish first-year university students were estimated using baseline (T1) and 12-month follow-up (T2) online surveys. Information about STBs, childhood/adolescence adversities, positive relationships, mental disorders, recent stressful experiences, and university sense of membership was assessed. Logistic regression analysis was used to study risk/protective factors of first-onset and persistence of suicidal ideation (SI). Results: A total of 1,248 respondents (58.9% response) were included. Mean age at baseline was 18.7 (SD = 1.3) and 56.0% were female. 7.3% reported 12-month SI at T2. Incidence of new SI cases was 3.4% and, among students with SI at T1, 21.2% also reported SI at T2 (persistence). Risk factors of T2 SI included 12-month mood disorder at T2 both without (aOR = 12.08 95% CI 5.45-26.80) or with (aOR = 7.2 95% CI 2.91-17.80) lifetime mood at T1, past lifetime suicide attempt (aOR = 8.79 95% CI 2.37-32.64) and plan without attempt (aOR = 4.72 95% CI 2.32-9.61), and 12-month physical or sexual assault (aOR = 3.28 95% CI 1.13-9.46). Twelve-month mood at T2 withoutT1 lifetime mood (aOR = 11.27 95% CI 3.02-42.14) and childhood/adolescence emotional abuse or neglect (aOR = 3.41 95% CI 1.10-10.57) or having been bullied (aOR = 3.2 95% CI 1.08-9.53) were associated with first-onset of SI. Twelve-month mood at T2 either without (aOR = 13.92 95% CI 3.76-51.59) or with (aOR = 8.03 95% CI 2.13-30.29) were associated to T2 SI persistence. University sense of membership was protective for overall 12-month SI at T2 (aOR = 0.25 95% CI 0.12-0.53 for middle tertile), first-onset SI (aOR = 0.1 95% 0.02-0.55 for middle tertile) and persistence (aOR = 0.3 95% CI 0.11-0.81 for middle tertile). Limitations: Analysis was based on self-report data focusing on SI only, and conclusions about the direction of the associations are limited. Conclusions: High proportion of SI suggests the need of suicide prevention strategies. The potential role of university sense of membership in reducing suicidal behaviour among university students deserves further investigation