Journal: Cell Reports

Article Title: Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease

doi: 10.1016/j.celrep.2022.111439

Figure Lengend Snippet: A gradient of cytokine-responsive transcriptional signatures stratifies patients with IBD into distinct molecular phenotypes (A) Activation of cytokine-responsive transcriptional signatures in whole colonic biopsies of patients with UC (UNIFI trial, n = 550) and colonic CD (UNITI2 trial, n = 126) (demographics shown in Table S1 ). Enrichment of cytokine-responsive transcriptional signatures was evaluated in the transcriptome of colonic biopsies using gene set variation analysis. A score of +1 suggests that all transcripts are upregulated, while a score of −1 suggests that all transcripts are downregulated (showing median and interquartile range [IQR], Mann Whitney test, ∗∗∗ p < 0.001). (B, C, and D) Gradient of cytokine-responsive transcriptional signature activation in IBD. Each column represents a single patient. The sum of all four scores per subject is also depicted as the total enrichment score (TES). Columns have been clustered by Euclidean distance (method: average, tree ordering: original, figure generated with ClustVis). Cohorts: UNITI2 (n = 126), UNIFI (UC, n = 550), and PROgECT (UC, n = 84). (E and F) Cytokine-responsive transcriptional signature association to clinical indices of human colonic inflammation in UC (UNIFI cohort, n = 550) and cCD (UNITI2 cohort, n = 126). All clinical data were collected prospectively as part of the trials’ protocol ( Feagan et al., 2016 ; Sands et al., 2019 ; Telesco et al., 2018 ).

Article Snippet: Human intestinal biopsies for whole transcriptome profiling (microarray) , Janssen Pharmaceuticals , UNITI2, NCT01369342 UNIFI, NCT02407236 PROgECT, NCT01988961.

Techniques: Activation Assay, MANN-WHITNEY, Generated

Journal: Cell Reports

Article Title: Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease

doi: 10.1016/j.celrep.2022.111439

Figure Lengend Snippet:

Article Snippet: Human intestinal biopsies for whole transcriptome profiling (microarray) , Janssen Pharmaceuticals , UNITI2, NCT01369342 UNIFI, NCT02407236 PROgECT, NCT01988961.

Techniques: Microarray, Recombinant, Cell Recovery, Sequencing, Software

Journal: JNCI Journal of the National Cancer Institute

Article Title: Differences in Genomic Profiles and Outcomes Between Thoracic and Adrenal Neuroblastoma

doi: 10.1093/jnci/djz027

Figure Lengend Snippet: Adrenal vs thoracic tumor copy number association analysis. A) Meta-analysis by nonoverlapping 1-Mb tiles. The y-axis reflects an inverse variance-weighted meta-analysis across four datasets—single nucleotide polymorphism (SNP) microarray, whole genome sequencing, whole exome sequencing, and gene panel sequencing cohorts—of average log-ratio (tumor normalized to normal) differences between adrenal vs thoracic cases divided by SD (z score). A positive z score (red) implies that the relative copy number is higher in adrenal vs thoracic cases and a negative z score (blue) implies the opposite. The inner dashed line illustrates the z score corresponding to a nominal P value cut point of .05, and the outer dotted line illustrates the z score corresponding to a multiple test-adjusted false discovery rate (FDR) cut point of 0.05. The 1-Mb bin containing MYCN is labeled, because it is the only focal copy number alteration to reach statistical significance. B) Meta-analysis by chromosome arm. “Avg Adrenal” and “Avg Thoracic” denote a weighted average copy number log-ratio for adrenal and thoracic cases, respectively. More positive/red values reflect regions of greater copy number gain and more negative/blue values reflect regions of greater copy number loss. From the difference of these values (Avg Difference), a z score and two-tailed P value were computed by inverse-variance meta-analysis. The FDR was controlled by the Benjamini-Hochberg method. Results with multiple test-adjusted statistical significance at FDR less than 0.05 are bolded.

Article Snippet: Functional Genomic Associations With Neuroblastoma Site of Origin To evaluate the relationship of primary site with functional subclasses of neuroblastoma, we performed unsupervised hierarchical clustering on adrenal (n = 143) and thoracic (n = 19) cases with RNA expression profiling obtained by HuEx microarray, as well as adrenal (n = 128) and thoracic (N = 15) cases with DNA methylation profiling by Infinium microarray.

Techniques: Microarray, Sequencing, Labeling, Two Tailed Test

Journal: JNCI Journal of the National Cancer Institute

Article Title: Differences in Genomic Profiles and Outcomes Between Thoracic and Adrenal Neuroblastoma

doi: 10.1093/jnci/djz027

Figure Lengend Snippet: Unbiased clustering analysis of functional genomic and DNA methylation data in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohort. Heatmaps and hierarchical clustering for all adrenal and thoracic (A) HuEx RNA microarray samples and (B) DNA methylation microarray samples. Rows reflect independent patient profiles and columns reflect the 200 probesets with the highest variance after (A) log2 transformation of RNA probe intensity and (B) logit transformation of methylation beta values. Columns are mean-centered and normalized by SD (z score transformation) and illustrated on a blue-yellow scale. Additional colored boxes illustrate clinical annotations for each patient according to the legend (white = missing annotation).

Article Snippet: Functional Genomic Associations With Neuroblastoma Site of Origin To evaluate the relationship of primary site with functional subclasses of neuroblastoma, we performed unsupervised hierarchical clustering on adrenal (n = 143) and thoracic (n = 19) cases with RNA expression profiling obtained by HuEx microarray, as well as adrenal (n = 128) and thoracic (N = 15) cases with DNA methylation profiling by Infinium microarray.

Techniques: Functional Assay, DNA Methylation Assay, Microarray, Transformation Assay, Methylation