ABSTRACT
Obesity has reached epidemic proportions in the United States, but little is known about the mechanisms of weight gain and weight loss. Integration of omics data is becoming a popular tool to increase understanding in such complex phenotypes. Biomarkers come in abundance, but small sample size remains a serious limitation in clinical trials. In the present study, we developed a strategy to screen predictors from a multiomics, high-dimensional, and longitudinal dataset from a small cohort of 10 women with obesity who were provided an identical very-low calorie diet. Our proposal explores the combinatorial space of potential predictors from transcriptomics, microbiome, metabolome, fecal bile acids, and clinical data with the application of the first-order Spearman partial correlation coefficient. Two statistics are proposed for screening predictors, the partial association score, and the persistent significance. We applied our strategy to predict rates of weight loss in our sample of participants in a hospital metabolic facility. Our method reduced an initial set of 42,000 biomarker candidates to 61 robust predictors. The results show baseline fecal bile acids and regulation in RT-polymerase chain reaction as the most predictive data sources in forecasting the rate of weight-loss. In summary, the present study proposes a strategy based on nonparametric statistics for ranking and screening predictors of weight loss from a multiomics study. The proposed biomarker screening strategy warrants further translational clinical investigation in obesity and other complex clinical phenotypes.
Subject(s)
Multiomics , Weight Loss , Female , Humans , Obesity/genetics , Feces , Bile Acids and SaltsABSTRACT
Tape stripping is a non-invasive skin sampling technique, which has recently gained use for the study of the transcriptome of atopic dermatitis (AD), a common inflammatory skin disorder characterized by a defective epidermal barrier and perturbated immune response. Here, we performed BRB-seq-a low cost, multiplex-based, transcriptomic profiling technique-on tape-stripped skin from 30 AD patients and 30 healthy controls to evaluate the methods' ability to assess the epidermal AD transcriptome. An AD signature consisting of 91 differentially expressed genes, specific for skin barrier and inflammatory response, was identified. The gene expression in the outermost layers, stratum corneum and stratum granulosum, of the skin showed highest correlation between tape-stripped skin and matched full-thickness punch biopsies. However, we observed that low and highly variable transcript counts, probably due to low RNA yield and RNA degradation in the tape-stripped skin samples, were a limiting factor for epidermal transcriptome profiling as compared to punch biopsies. We conclude that deep BRB-seq of tape-stripped skin is needed to counteract large between-sample RNA yield variation and highly zero-inflated data in order to apply this protocol for population-wide screening of the epidermal transcriptome in inflammatory skin diseases.
Subject(s)
Dermatitis, Atopic , Dermatitis, Atopic/metabolism , Epidermis/metabolism , Humans , RNA/metabolism , Skin/metabolism , TranscriptomeABSTRACT
Introdução:A infecção pelo HIV pode levar à imunossupressão progressiva e resultar em um complexo de infecções relacionadas à AIDS e outras manifestações nos indivíduos acometidos. Dados do Boletim Epidemiológico AIDS 2012, relatam, de 1980 a 2010, 241.662 óbitos por AIDS no Brasil. Niterói, no estado do Rio de Janeiro, é um município de médio porte, com cerca de 500 mil habitantes e excelentes indicadores socioeconômicos e culturais.Objetivo:Avaliar a possível relação de sazonalidade existente entre a distribuição temporal da demanda e da positividade de testes sorológicos anti-HIV no Laboratório Central de Saúde Pública Miguelote Viana (LCSPMV), de Niterói, Rio de Janeiro.Métodos:Trata-se de um estudo transversal analítico de série temporal. Foram analisados os dados dedemanda, de positividade dos exames anti-HIV e dos dias trabalhados, coletados de um banco de dados referentes ao período de 2005 a 2010. Os dados foramavaliados estatisticamente por uma série temporal e testes de hipótese para tendência e sazonalidade. O LCSPMV é referência na dosagem de carga viral e níveis deCD4 para todas as unidades de saúde da rede pública de Niterói e também atende à população oriunda dos municípios que fazem parte da Região MetropolitanaII.Esta é uma pesquisa inovadora, visto que ainda não foram encontrados artigos que correlacionem aumentos/diminuições das demandas de exames anti-HIV com osrespectivos meses dos anos.Resultados:No período de janeiro de 2005 até dezembro de 2010, registramos 64.505 exames sorológicos anti-HIV, sendo em 2005,17,44% (11.252); em 2006, 16,36% (10.557); em 2007, 17,81% (11.494); em 2008, 17,12% (11.046); em 2009, 16,20% (10.452); e em 2010,15,04%(9.704).
Introduction:HIV infection can lead to a progressive immunosuppression and result in an AIDS-related infections complex and other manifestations in affected individuals. Data from the AIDS 2012 Epidemiological Bulletin from 1980 to 2010 reported 241,662 deaths from AIDS in Brazil. Niterói, in Rio de Janeiro State, isa medium-sized city, of 500,000 in habitants approximately and expressive socioeconomic and cultural indicators.Objective:To evaluate the relations hip between seasonal demand and positivity of anti-HIV tests in the Miguelote Viana Public Health Central Laboratory located in Niterói.Methods:This is a temporal series analytical cross-sectional study. Anti-HIV tests demand, positivity and days worked by Miguelote Viana Public Health Central Laboratory were analyzed froma database for the period from 2005 to 2010. Data was then statistically evaluated through a temporal seriesand hypothesis testing on tendency and seasonality.Miguelote Viana Public Health Central Laboratory is a reference center for the dosage of viral load and CD4 levels for all public health units of Niterói; also attending to the population of cities in Metropolitan Region II. This is an innovative research, since articles that relate anti-HIV tests demand increase/decrease with the respective months of the year have not been found yet. As a result, we present graphs, tables and charts.Results:From January 2005 to December 2010,we have registered 64,505 serological tests for HIV, as follows: 17.44% (11,252) in 2005; 16.36% (10,557) in 2006; 17.81% (11,494) in 2007; 17.12% (11,046)in 2008; 16.20% (10,452) in 2009; and 15.04% (9,704) in 2010. In annual average, the days worked per month were as follows: 20in 2005; 19.5 in 2006; 19.8 in2007; 19.6 in 2008; 19.7 in 2009 and 19.3 in 2010. The monthly average of days worked in the six years studied was: 21 in Jan; 17.3 in February; 21.6 in March;17.3 in April; 20 in May; 18.6 in June; 21.6 in July; 22 in August; 20.3 in September; 20.3 in October; 17.3 in November and 18.6 days in December. The annual average of positivity in absolute numbers was as follows: 42.6 in 2005; 44.0 in 2006; 38.3 in 2007; 32.8 in 2008; 24.25 in 2009and 25.25 in 2010. The average positivity per month in the six years studied was the following: 39.3 in January; 29.3 in February; 40.8 in March; 31.8 in April; 31.1 in May; 34.6 in June; 33.8 inJuly; 38.6 in August; 35.0 in September; 34.8 in October; 31.5 in November and 33.6 in December. The average percentage of positivity per month was as follows:January (4.35), February (3.85), March (3.95), April (3.88), May (3.56), June (2.34), July (3.54), August (3.80), September (3.79), October (3.60), November (3.92)and December (3.75). In the studied period (2005-2010), Carnival holidays occurred in the month of February, on the following days: 8, 28, 20, 5, 24 and 16,respectively.Conclusion:We observed no seasonal relation between demand and positivity of anti-HIV tests carried out at Miguelote Viana Public Health Central Laboratory. A significant statistical decrease occurred in both anti-HIV tests demand and positivity during the studied years of the 2005-2010 series.
