Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease

Palmer, Nathan; Silvester, Jocelyn A.; Lee, Jessica J.; Beam, Andrew L.; Fried, Inbar; Valtchinov, Vladimir I.; Rahimov, Fedik; Kong, Sek Won; Ghodoussipour, Saum; Hood, Helen C.; Bousvaros, Athos; Grand, Richard J.; Kunkel, Louis M.; Kohane, Isaac S.

doi:10.1371/journal.pone.0222952

Cited by 36 publications

(50 citation statements)

References 46 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we were limited on the choice of groups to classify by data availability, as we could only find three gene expression data sets obtained from colonic samples of UC and CD patients in GEO (GSE1152, GSE75214 and GSE126124). As children samples were transcriptionally profiled for GSE126124 48 instead of adults ones, we decided that the age difference could introduce extra biological variation in the expression data unrelated to UC. That left us with only two data sets which were not enough to train the model with multiple data sets and have at least one hold-out data set for validation.…”

Section: Discussionmentioning

confidence: 99%

Detecting ulcerative colitis from colon samples using efficient feature selection and machine learning

Khorasani

Usefi

Peña‐Castillo

2020

Sci Rep

View full text Add to dashboard Cite

Ulcerative colitis (UC) is one of the most common forms of inflammatory bowel disease (IBD) characterized by inflammation of the mucosal layer of the colon. Diagnosis of UC is based on clinical symptoms, and then confirmed based on endoscopic, histologic and laboratory findings. Feature selection and machine learning have been previously used for creating models to facilitate the diagnosis of certain diseases. In this work, we used a recently developed feature selection algorithm (DRPT) combined with a support vector machine (SVM) classifier to generate a model to discriminate between healthy subjects and subjects with UC based on the expression values of 32 genes in colon samples. We validated our model with an independent gene expression dataset of colonic samples from subjects in active and inactive periods of UC. Our model perfectly detected all active cases and had an average precision of 0.62 in the inactive cases. Compared with results reported in previous studies and a model generated by a recently published software for biomarker discovery using machine learning (BioDiscML), our final model for detecting UC shows better performance in terms of average precision.

show abstract

Section: Discussionmentioning

confidence: 99%

Detecting ulcerative colitis from colon samples using efficient feature selection and machine learning

Khorasani

Usefi

Peña‐Castillo

2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Importantly, it can be used in addition to the clinical trial data for training the host-microbiome-Mtb model described subsequently. 38 of IBD cases vs controls in this study for Day 56 vs Baseline. Multi-omics-constrained mathematical modeling to decouple the contribution to peripheral inflammatory signature of intestinal microbiota and Mtb.…”

Section: Longitudinal Profiling In An Early Bactericidal Activity Hrzmentioning

confidence: 92%

“…NTZ is found only to exacerbate four. D, E. Effect of HRZE and NTZ on blood gene expression for a set of IBD-associated genes from Palmer, et al 38 . Both drugs, HRZE in D and NTZ in E cause different genes to either renormalize (HRZE 66, NTZ 34) or exacerbate (HRZE 55, NTZ 21).…”

Section: Hrze and Ntz Uniquely Affect Host Peripheral Gene Expressionmentioning

confidence: 99%

“…Because of the disruption in microbiome composition in the absence of a change in disease severity observed in NTZ-treated people, we hypothesized that there may be other subsets of host genes that are linked to microbiome-dependent immunity that could be responsive to the observed antimicrobial perturbations. To test this, considering the already well-established link between microbiome dysbiosis and autoinflammatory conditions such as Inflammatory Bowel Disease (IBD) 39 , we selected a recently published panel of 880 genes differentially expressed in colon biopsies from IBD patients and asymptomatic controls 38 . Of these 880 genes, 364 were detected in our dataset (expected given that we are profiling whole blood transcriptomics, rather than colon biopsy tissue).…”

Section: Hrze and Ntz Uniquely Affect Host Peripheral Gene Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Intestinal microbiome composition influences the peripheral inflammatory state during treatment of human tuberculosis

Wipperman¹,

Bhattarai²,

Vorkas³

et al. 2020

Preprint

View full text Add to dashboard Cite

Although the composition of the intestinal microbiota influences systemic immune responses, the contribution of this relationship to infectious disease pathogenesis and to the resolution of infectious diseases by antibiotic therapy is poorly understood. This question is rarely examined in humans due to the difficulty in dissociating the immunologic effects of antibiotic-induced pathogen clearance and salutary microbiome alteration. To address these questions in the context of Tuberculosis, we analyzed three independent human datasets from Haiti (two longitudinal treatment and one cross-sectional control), a prototypical infection remarkable for chronic inflammation, in which we had measured sputum TB bacterial load, gut microbiota composition, and peripheral blood transcriptomics. Using data from the longitudinal datasets combined with inflammatory pathway enrichment analysis, we determined that antibiotic treatment of TB, despite significantly perturbing the gut microbiota, dampens the proinflammatory signature characteristic of active TB. Contrarily, an investigational TB treatment that failed to clear TB, but that caused similar microbiota perturbations, exacerbated peripheral inflammation. To decouple the effects of antibiotic induced changes in the microbiota from Mtb sterilization as predictors of normalization of TB associated inflammation, we applied random forest regression to the microbiome-transcriptome-sputum data from the two longitudinal datasets. We found inflammatory renormalization is positively affected by both pathogen sterilization and by the abundance of health-associated Cluster IV and Cluster XIa Clostridia. Oppositely, increases in the abundance of commonly known pathobionts such as Bacilli and Proteobacteria clusters predict inflammatory exacerbation. We independently investigated and validated these microbiota-peripheral inflammatory signature associations by applying machine learning to the peripheral gene expression and microbiota profiling in an independent human cohort of 52 healthy control individuals. Together, our findings indicate that antibiotic-induced reduction in pathogen burden and changes in the microbiome are independently associated with treatment-induced changes of the inflammatory response of active TB, and more broadly indicate that response to antibiotic therapy may be a combined effect of pathogen killing and microbiome driven immunomodulation. Our results provide support to the hypothesis that there exists clear links between microbiome composition and host peripheral gene expression in humans that can be biologically elucidated using common and well validated molecular pathway analyses.

show abstract

“…In humans, peripheral blood cells (PBCs) are widely used to check the health status by analyzing the gene expression pattern in peripheral blood and to predict the same gene expression in non-accessible tissues like brain, liver, gonad, kidney, lungs etc. In various human studies, expression of many health status indicative genes in PBCs show significant correlations to the respective gene expression in different other organ tissues [ 35 , 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

The Relationship between the Expression of Fatty Acyl Desaturase 2 (fads2) Gene in Peripheral Blood Cells (PBCs) and Liver in Gilthead Seabream, Sparus aurata Broodstock Fed a Low n-3 LC-PUFA Diet

Ferosekhan

Türkmen

et al. 2020

Life

View full text Add to dashboard Cite

The principle aim of this study is to elucidate the relationship between the fatty acid desaturase 2 gene (fads2) expression pattern in peripheral blood cells (PBCs) and liver of gilthead seabream (GSB), Sparus aurata broodstock in order to determine the possible use of fads2 expression as a potential biomarker for the selection of broodstock. This selection could be utilized for breeding programs aiming to improve reproduction, health, and nutritional status. Passive Integrated Transponder (PIT)-tagged GSB broodstock (Male-1.22 ± 0.20 kg; 44.8 ± 2 cm and female-2.36 ± 0.64 kg; 55.1 cm) were fed a diet containing low levels of fish meal and fish oil (EPA 2.5; DHA 1.7 and n-3 LC-PUFA 4.6% TFA) for one month. After the feeding period, fads2 expression in PBCs and liver of both male and female broodstock were highly significantly correlated (r = 0.89; p < 0.001). Additionally, in male broodstock, liver fads2 expression was significantly correlated (p < 0.05) to liver contents in 16:0 (r = 0.95; p = 0.04) and total saturates (r = 0.97; p = 0.03) as well as to 20:3n–6/20:2n–6 (r = 0.98; p = 0.02) a Fads2 product/precursor ratio. Overall, we found a positive and significant correlation between fads2 expression levels in the PBCs and liver of GSB broodstock. PBCs fads2 expression levels indicate a strong potential for utilization as a non-invasive method to select animals having increased fatty acid bioconversion capability, better able to deal with diets free of fish meal and fish oil.

show abstract

Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease

Cited by 36 publications

References 46 publications

Detecting ulcerative colitis from colon samples using efficient feature selection and machine learning

Detecting ulcerative colitis from colon samples using efficient feature selection and machine learning

Intestinal microbiome composition influences the peripheral inflammatory state during treatment of human tuberculosis

The Relationship between the Expression of Fatty Acyl Desaturase 2 (fads2) Gene in Peripheral Blood Cells (PBCs) and Liver in Gilthead Seabream, Sparus aurata Broodstock Fed a Low n-3 LC-PUFA Diet

Contact Info

Product

Resources

About