The Human Genomic Response to Severe Traumatic Injury: An Interactive Website for Exploring Gene Expression and Clinical Outcomes


"Inflammation and the Host Response to Injury", a Large-Scale Collaborative Project Awards (Glue Grants) initiative of the National Institute of General Medical Sciences awarded to Massachusetts General Hospital to include a large number of participating investigators and multi-institutional collaborations.

Introduction and Background

The Inflammation and Host Response to Injury investigators agreed that the most important biological problem to tackle in the area of injury research centered on the innate inflammatory response, and specifically, to improve our systems level understanding of the key regulatory elements, and their relative roles and importance that drive the host's response to serious injury and its accompanying severe systemic inflammation. This website represents supplementary information for our initial main report describing the leukocyte transcriptome in trauma and burn patients, and healthy subjects receiving low-dose bacterial endotoxin to compare the impact of these stressors. The website contains the genomic and clinical data from the trauma patients and their respective controls, and is an open-access tool for the scientific community to explore the relationship between longitudinal whole blood leukocyte genomic expression and clinical attributes in severely injured trauma patients.

The data set is obtained from both 35 healthy subjects and 167 severely injured patients, ages 16-55, who experienced blunt trauma and required aggressive resuscitation, including blood products. The study attributes include:

• 167 patients
• 35 healthy subjects
• 7 clinical sites
• Patient blood samples taken 12 hours and days 1, 4, 7, 14, 21, 28 after injury
• Blood leukocyte genome wide expression (Affymetrix U133+ v2 GeneChip™)
• 15 clinical attributes, including demographics and outcomes

In addition, the 167 trauma patients were stratified into two groups based on their clinical trajectories and outcomes. A full description of the two groups is contained in the J Exp Med publication. Briefly, patients who experienced an Uncomplicated Recovery (n=55) were defined as having no multiorgan failure defined as a Marshall score < 6, and a Time to Recovery in less than 5 days. In contrast, a Complicated Recovery (n=41) was defined as those patients with Marshall scores > 6 and a Time to Recovery on or after day 14. For more information regarding study design, please refer to the original manuscript.

Instructions

The website contains a flat database that links genome-wide expression data from whole blood leukocytes to the clinical attributes in the 167 severely trauma patients, based on the experimental approaches described in the publication. In addition, the website contains links to external resources for studying gene ontologies and pathways. The website can be used to:

(1) to view the expression of an individual gene or probe set, and explore its relationship to clinical demographics or outcomes; (2) to examine the association between clinical demographics or outcomes and gene expression patterns, (3) to explore different patterns of gene expression (clusters) after severe trauma, and how those patterns vary with clinical outcomes.

To explore the expression of individual genes and probe sets, click here
Investigating specific genes or probe sets to see how the expression changes over the time course associated with clinical attributes and outcomes

To examine the relationship between clinical attributes and gene expression, click here
Investigating the relationship of measured clinical attributes and outcomes along with corresponding genomic expression

Click here for the interactive Figure 1 from the publication which summarizes the genome wide expression response from the entire 167 patients and 35 control subjects. Figure 1 contains a heat map of the 5,136 genes whose expression in the trauma subjects was significantly different from the expression of the 35 control subjects. The Figure is arranged so that the 5,136 genes have been arranged in 30 bins (clusters) based upon the similar patterns of expression over time. Columns represent individual samples obtained from control subjects or severely injured patients at different time-points between 12 hrs and 28 days. Each row represents a single gene and the colors indicate variance normalized expression with red being indicative of expression above the mean, white at the mean, and blue below the mean for that gene.

• View individual genes whose expression differs with time, clustered by their patterns of expression.

Disclaimers

The website is a tool to explore the clinical and genomic dataset contained in the publication, using intuitive and friendly tools. This website is copyrighted and is the property of Massachusetts General Hospital. The Glossary and Methods contains a detailed explanation of the statistical and bioinformational approaches used in the website, as well as definitions. The data employs statistical approaches and software tools that were current as of March 15, 2011, but may have been superceded. Some links to external sites may require prior registration.

Unrestricted access to the dataset, including individual expression values, requires consortium membership and IRB approval from your local institution. For detailed instructions, follow the links at www.gluegrant.org.






Data and Analysis Description

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