Summary: Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signaling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-seq. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients.
Overall Design: Total RNA-seq from knee and hip joints in rheumatoid arthritis (RA)
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Species: |
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Tissue: |
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Healthy Condition: |
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Growth Protocol: | - |
Treatment Protocol: | - |
Extract Protocol: | Total RNA was extracted and the quality of all samples was evaluated using an Agilent Bioanalyzer. The samples had an average RNA Integrity Number (RIN) of 9.4 with a minimum of 7.5. |
Library Construction Protocol: | Libraries were pooled and sequenced with an Illumina HiSeq 2000 with paired-end 100 bp flow cell. |
Molecule Type: | rRNA- RNA |
Library Source: | |
Library Layout: | PAIRED |
Library Strand: | Forward |
Platform: | ILLUMINA |
Instrument Model: | Illumina HiSeq 2000 |
Strand-Specific: | Specific |
Data Resource | GEN Sample ID | GEN Dataset ID | Project ID | BioProject ID | Sample ID | Sample Name | BioSample ID | Sample Accession | Experiment Accession | Release Date | Submission Date | Update Date | Species | Race | Ethnicity | Age | Age Unit | Gender | Source Name | Tissue | Cell Type | Cell Subtype | Cell Line | Disease | Disease State | Development Stage | Mutation | Phenotype | Case Detail | Control Detail | Growth Protocol | Treatment Protocol | Extract Protocol | Library Construction Protocol | Molecule Type | Library Layout | Strand-Specific | Library Strand | Spike-In | Strategy | Platform | Instrument Model | Cell Number | Reads Number | Gbases | AvgSpotLen1 | AvgSpotLen2 | Uniq Mapping Rate | Multiple Mapping Rate | Coverage Rate |
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