Assessing the human immune system through blood transcriptomics

Chaussabel, Damien; Pascual, Virginia; Banchereau, Jacques

doi:10.1186/1741-7007-8-84

Cited by 236 publications

(213 citation statements)

References 143 publications

(164 reference statements)

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“…Whole blood measurements, however, provide us with a practical, repeatable sampling measure in pigs, as well as a more global view of the response. Whole blood transcriptomics have been highlighted as a useful measure of biomarkers for the immune response to disease in humans, 60 and their capabilities in livestock are beginning to be elucidated.…”

Section: Blood Transcriptomic Patterns Indicate Regulatory Pathway DImentioning

confidence: 99%

Salmonella entericaserovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes

et al. 2014

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Christopher, "Salmonella enterica serovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes" (2014 AbstractFoodborne salmonellosis costs the US $2.7 billion/year, including $100.0 million in annual losses to pork producers. Pigs colonized with Salmonella are usually asymptomatic with varied severity and duration of fecal shedding. Thus, understanding the responses that result in less shedding may provide a mechanism for control. Fifty-four pigs were inoculated with Salmonella enterica serovar Typhimurium (ST) and clinical signs, fecal ST shedding, growth performance, peripheral cytokines and whole blood gene expression were measured. Persistently shedding (PS) pigs had longer pyrexia and elevated serum IL-1b, TNF-a and IFN-g compared with low shedding (LS) pigs, while LS pigs had brief pyrexia, less shedding that decreased more rapidly and greater serum CXCL8 than PS pigs. The PS pigs up-regulated genes involved with the STAT1, IFNB1 and IFN-g networks on d 2, while up-regulation of genes involved in immune response regulation were only detected in LS pigs. This is the first study to examine host responses to ST infection at a clinical, performance, cytokine and transcriptomic level. The results indicated that pigs with different shedding outcomes developed distinct immune responses within the first 2 d of ST infection, and elucidated alternative mechanisms that could be targeted to reduce Salmonella shedding and spread.

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Section: Blood Transcriptomic Patterns Indicate Regulatory Pathway DImentioning

confidence: 99%

Salmonella entericaserovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes

et al. 2014

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“…Screening populations based on direct detection of the causative pathogen can be problematic, because readily-accessible specimens such as blood often contain little or no pathogen, particularly at pre-symptomatic stages of disease. However, host response to the pathogen is rapid, robust, and evident in blood throughout the course of infection 1 . Thus, screening populations based on host response biomarkers in blood is an attractive approach, especially if the biomarkers are nucleic acids (NA), as these can be efficiently recovered from tiny specimens (e.g., fingerstick draws) and detected with tremendous sensitivity and specificity via PCR.…”

Section: Overview Of the Problem And Our Solutionmentioning

confidence: 99%

“…In recent years, brute-force SGS of clinical specimens (e.g., conventional RNASeq) has led to successful identification of disease biomarkers. 1 However, this approach is slow, labor-and compute-intensive, and expensive, primarily because sequencing bandwidth is dominated by NA that are highly abundant (e.g., in Ref. 8, 75% of reads derived from 7% of expressed transcripts) and/or present at similar levels regardless of disease state (in most experiments, >90% of transcripts are not differentially expressed to a statistically significant degree).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, NA profiles are informationrich (e.g., mRNA: >100,000 varieties, >10,000X abundance range, in human WBC), and with microarrays it became feasible to conduct high-throughput searches for NA biomarkers of disease. A decade of attempts yielded some notable successes 1,[5][6][7] , including diagnostics in clinical use today (e.g., MammaPrint, Oncotype DX). Success rates might have been higher were it not for the low sensitivity and narrow dynamic range of microarrays, which precludes reliable detection of low-abundance NA and accurate quantitation of NA at each end of the abundance spectrum; these constraints cripple attempts to identify NA present at low levels in one specimen (e.g., healthy blood) and high in another (e.g., infected blood).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of host response signatures of infection.

Branda¹,

Sinha²,

Bent³

2013

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Biological weapons of mass destruction and emerging infectious diseases represent a serious and growing threat to our national security. Effective response to a bioattack or disease outbreak critically depends upon efficient and reliable distinguishing between infected vs healthy individuals, to enable rational use of scarce, invasive, and/or costly countermeasures (diagnostics, therapies, quarantine). Screening based on direct detection of the causative pathogen can be problematic, because culture-and probe-based assays are confounded by unanticipated pathogens (e.g., deeply diverged, engineered), and readily-accessible specimens (e.g., blood) often contain little or no pathogen, particularly at presymptomatic stages of disease. Thus, in addition to the pathogen itself, one would like to detect infection-specific host response signatures in the specimen, preferably ones comprised of nucleic acids (NA), which can be recovered and amplified from tiny specimens (e.g., fingerstick draws). Proof-ofconcept studies have not been definitive, however, largely due to use of sub-optimal sample preparation and detection technologies. For purposes of pathogen detection, Sandia has developed novel molecular biology methods that enable selective isolation of NA unique to, or shared between, complex samples, followed by identification and quantitation via Second Generation Sequencing (SGS). The central hypothesis of the current study is that variations on this approach will support efficient identification and verification of NA-based host response signatures of infectious disease. To test this hypothesis, we reengineered Sandia's sophisticated sample preparation pipelines, and developed new SGS data analysis tools and strategies, in order to pioneer use of SGS for identification of host NA correlating with infection. Proof-of-concept studies were carried out using specimens drawn from pathogen-infected non-human primates (NHP). This work provides a strong foundation for large-scale, highly-efficient efforts to identify and verify infection-specific host NA signatures in human populations. 4 AcknowledgementsWe thank Matt Reed and Katie Overheim (Lovelace Respiratory Research Institute, Albuquerque, NM) for providing us with the pathogen-infected NHP specimens that were the focus of this study. We thank

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“…Transcriptomics is a powerful technique, which can be used for detecting new therapeutic biomarkers and targets in the ield of infectious diseases [31,32]. Several studies of gene expression in sepsis on a large scale have been performed.…”

Section: Transcriptomics In Sepsismentioning

confidence: 99%