Differential Gene Expression Associated with BMI, Gender, and IBS-subtype in Human White Blood Cells: Results from a Custom 250-plex Nanostring Probe Panel

Abstract

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Predictive Classification of IBS-subtype: Performance of a 250-gene RNA expression panel vs. Complete Blood Count (CBC) profiles under a Random Forest model

“…White Blood Cell (“Buffy Coat”) fractions were also collected, and RNA expression profiles were developed for the same clinical cohort using a 250-gene Nanostring gene expression panel (Robinson 2019). Both the raw and normalized Nanostring expression data and gene list and probe details of the 250-gene Nanostring probe panel “ImmunoGC” are available in the NCBI Gene Expression Omnibus (GEO) database.…”