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The biologic basis of clinical heterogeneity in juvenile idiopathic arthritis.

Eng SW, Duong TT, Rosenberg AM, Morris Q, Yeung RS, REACCH OUT and BBOP Research Consort - (2014)

Bottom Line: The new patient classifications resolved major differences between patient subpopulations better than International League of Associations for Rheumatology subtypes.This new schema was conserved in an independent validation cohort.Our analytical framework enabled the recovery of unique patterns from small cohorts and addresses a major challenge, patient numbers, in studying rare diseases.

View Article: PubMed Central - PubMed

Affiliation: The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

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Related in: MedlinePlus

Relationships between clusters and ILAR subtypes. The circular plot depicts relationships and patient compositions of each new cluster (left) and ILAR subtype (right). Individual patient scores on each of the 4 principal components (PCs) are depicted in the outermost layer (a), with the heatmap corresponding to the scores for each PC shown at lower left. Each cluster and ILAR subtype is depicted by a color or shade of gray, respectively, in the second layer (b). The ILAR subtype composition (shades of gray) of each cluster and the cluster composition (colors) of each ILAR subtype are depicted in the third layer (c). Colored ribbons link clusters and ILAR subtypes. Numbers of patients are proportional to the width of the ribbons. Thicker ribbons indicate more patients shared between clusters and ILAR subtypes. See Figure 2 for other definitions.
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fig03: Relationships between clusters and ILAR subtypes. The circular plot depicts relationships and patient compositions of each new cluster (left) and ILAR subtype (right). Individual patient scores on each of the 4 principal components (PCs) are depicted in the outermost layer (a), with the heatmap corresponding to the scores for each PC shown at lower left. Each cluster and ILAR subtype is depicted by a color or shade of gray, respectively, in the second layer (b). The ILAR subtype composition (shades of gray) of each cluster and the cluster composition (colors) of each ILAR subtype are depicted in the third layer (c). Colored ribbons link clusters and ILAR subtypes. Numbers of patients are proportional to the width of the ribbons. Thicker ribbons indicate more patients shared between clusters and ILAR subtypes. See Figure 2 for other definitions.

Mentions: This definitive difference in homogeneity was clear when we displayed patient PC scores (heatmaps), grouped by cluster and ILAR subtype, and linkages (ribbons) between these 2 classification schemes using a Circos diagram (Figure 3). Homogeneous patterns were clearly evident in PC scores for each cluster on the left compared to the heterogeneous patterns for each ILAR subtype on the right. Additionally, oligoarthritis separated into all 5 clusters regardless of segregation into persistent or extended oligoarthritis (results not shown). Clinically meaningful patterns and linkages were visible; cluster I, which mostly corresponded to an ERA subset, and a large subset of cluster III, which corresponded to RF-negative polyarthritis, suggested that the clustering recapitulated expert-derived patient subtypes while stratifying patients more homogeneously.


The biologic basis of clinical heterogeneity in juvenile idiopathic arthritis.

Eng SW, Duong TT, Rosenberg AM, Morris Q, Yeung RS, REACCH OUT and BBOP Research Consort - (2014)

Relationships between clusters and ILAR subtypes. The circular plot depicts relationships and patient compositions of each new cluster (left) and ILAR subtype (right). Individual patient scores on each of the 4 principal components (PCs) are depicted in the outermost layer (a), with the heatmap corresponding to the scores for each PC shown at lower left. Each cluster and ILAR subtype is depicted by a color or shade of gray, respectively, in the second layer (b). The ILAR subtype composition (shades of gray) of each cluster and the cluster composition (colors) of each ILAR subtype are depicted in the third layer (c). Colored ribbons link clusters and ILAR subtypes. Numbers of patients are proportional to the width of the ribbons. Thicker ribbons indicate more patients shared between clusters and ILAR subtypes. See Figure 2 for other definitions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4282094&req=5

fig03: Relationships between clusters and ILAR subtypes. The circular plot depicts relationships and patient compositions of each new cluster (left) and ILAR subtype (right). Individual patient scores on each of the 4 principal components (PCs) are depicted in the outermost layer (a), with the heatmap corresponding to the scores for each PC shown at lower left. Each cluster and ILAR subtype is depicted by a color or shade of gray, respectively, in the second layer (b). The ILAR subtype composition (shades of gray) of each cluster and the cluster composition (colors) of each ILAR subtype are depicted in the third layer (c). Colored ribbons link clusters and ILAR subtypes. Numbers of patients are proportional to the width of the ribbons. Thicker ribbons indicate more patients shared between clusters and ILAR subtypes. See Figure 2 for other definitions.
Mentions: This definitive difference in homogeneity was clear when we displayed patient PC scores (heatmaps), grouped by cluster and ILAR subtype, and linkages (ribbons) between these 2 classification schemes using a Circos diagram (Figure 3). Homogeneous patterns were clearly evident in PC scores for each cluster on the left compared to the heterogeneous patterns for each ILAR subtype on the right. Additionally, oligoarthritis separated into all 5 clusters regardless of segregation into persistent or extended oligoarthritis (results not shown). Clinically meaningful patterns and linkages were visible; cluster I, which mostly corresponded to an ERA subset, and a large subset of cluster III, which corresponded to RF-negative polyarthritis, suggested that the clustering recapitulated expert-derived patient subtypes while stratifying patients more homogeneously.

Bottom Line: The new patient classifications resolved major differences between patient subpopulations better than International League of Associations for Rheumatology subtypes.This new schema was conserved in an independent validation cohort.Our analytical framework enabled the recovery of unique patterns from small cohorts and addresses a major challenge, patient numbers, in studying rare diseases.

View Article: PubMed Central - PubMed

Affiliation: The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

Show MeSH
Related in: MedlinePlus