Dataset Information

Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

ABSTRACT: Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling. Methods that support this intensive sampling need to be developed and validated as feasible. To this end, we describe here a detailed approach that was applied in a study of 15 healthy adults, who were immunized with hepatitis B vaccine. Sampling included ~350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a ~7-month period, enabling comprehensive analysis of the immune response at the molecular level, including single cell and tissue sample analysis. Samples were collected for analysis of immune phenotyping, whole blood and single cell gene expression, proteomics, lipidomics, epigenetics, whole blood response to key immune stimuli, cytokine responses, in vitro T cell responses, antibody repertoire analysis and the microbiome. Data integration was undertaken using different approaches-NetworkAnalyst and DIABLO. Our results demonstrate that such intensive sampling studies are feasible in healthy adults, and data integration tools exist to analyze the vast amount of data generated from a multi-omics systems biology approach. This will provide the basis for a better understanding of vaccine-induced immunity and accelerate future rational vaccine design.

SUBMITTER: Ben-Othman R

PROVIDER: S-EPMC7672042 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

Ben-Othman Rym R Cai Bing B Liu Aaron C AC Varankovich Natallia N He Daniel D Blimkie Travis M TM Lee Amy H AH Gill Erin E EE Novotny Mark M Aevermann Brian B Drissler Sibyl S Shannon Casey P CP McCann Sarah S Marty Kim K Bjornson Gordean G Edgar Rachel D RD Lin David Tse Shen DTS Gladish Nicole N Maclsaac Julia J Amenyogbe Nelly N Chan Queenie Q Llibre Alba A Collin Joyce J Landais Elise E Le Khoa K Reiss Samantha M SM Koff Wayne C WC Havenar-Daughton Colin C Heran Manraj M Sangha Bippan B Walt David D Krajden Mel M Crotty Shane S Sok Devin D Briney Bryan B Burton Dennis R DR Duffy Darragh D Foster Leonard J LJ Mohn William W WW Kobor Michael S MS Tebbutt Scott J SJ Brinkman Ryan R RR Scheuermann Richard H RH Hancock Robert E W REW Kollmann Tobias R TR Sadarangani Manish M

Frontiers in immunology 20201104

Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to ...[more]

PMID: 33250895

Similar Datasets

Project description:BackgroundBreast cancer is worldwide the second most common type of cancer after lung cancer. Plasma proteome profiling may have a higher chance to identify protein changes between plasma samples such as normal and breast cancer tissues. Breast cancer cell lines have long been used by researches as model system for identifying protein biomarkers. A comparison of the set of proteins which change in plasma with previously published findings from proteomic analysis of human breast cancer cell lines may identify with a higher confidence a subset of candidate protein biomarker.ResultsIn this study, we analyzed a liquid chromatography (LC) coupled tandem mass spectrometry (MS/MS) proteomics dataset from plasma samples of 40 healthy women and 40 women diagnosed with breast cancer. Using a two-sample t-statistics and permutation procedure, we identified 254 statistically significant, differentially expressed proteins, among which 208 are over-expressed and 46 are under-expressed in breast cancer plasma. We validated this result against previously published proteomic results of human breast cancer cell lines and signaling pathways to derive 25 candidate protein biomarkers in a panel. Using the pathway analysis, we observed that the 25 "activated" plasma proteins were present in several cancer pathways, including 'Complement and coagulation cascades', 'Regulation of actin cytoskeleton', and 'Focal adhesion', and match well with previously reported studies. Additional gene ontology analysis of the 25 proteins also showed that cellular metabolic process and response to external stimulus (especially proteolysis and acute inflammatory response) were enriched functional annotations of the proteins identified in the breast cancer plasma samples. By cross-validation using two additional proteomics studies, we obtained 86% and 83% similarities in pathway-protein matrix between the first study and the two testing studies, which is much better than the similarity we measured with proteins.ConclusionsWe presented a 'systems biology' method to identify, characterize, analyze and validate panel biomarkers in breast cancer proteomics data, which includes 1) t statistics and permutation process, 2) network, pathway and function annotation analysis, and 3) cross-validation of multiple studies. Our results showed that the systems biology approach is essential to the understanding molecular mechanisms of panel protein biomarkers.

Dataset Information

Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

Publications

Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets