T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus
Publication Date
November 06, 2015
Journal
PLOS ONE
Authors
Sean J. Bradley, Abel Suarez Fueyo, David R. Moss, Vasileios C. Kyttaris, et al
Volume
10
Issue
11
Pages
e0141171
DOI
https://dx.plos.org/10.1371/journal.pone.0141171
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0141171
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26544975
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636226
Europe PMC
http://europepmc.org/abstract/MED/26544975
Web of Science
000364398700018
Scopus
84952313223
Mendeley
http://www.mendeley.com/research/t-cell-transcriptomes-describe-patient-subtypes-systemic-lupus-erythematosus
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Mendeley | Further Information

{"title"=>"T cell transcriptomes describe patient subtypes in systemic lupus erythematosus", "type"=>"journal", "authors"=>[{"first_name"=>"Sean J.", "last_name"=>"Bradley", "scopus_author_id"=>"57027074100"}, {"first_name"=>"Abel", "last_name"=>"Suarez-Fueyo", "scopus_author_id"=>"50162450300"}, {"first_name"=>"David R.", "last_name"=>"Moss", "scopus_author_id"=>"57027064300"}, {"first_name"=>"Vasileios C.", "last_name"=>"Kyttaris", "scopus_author_id"=>"6507128058"}, {"first_name"=>"George C.", "last_name"=>"Tsokos", "scopus_author_id"=>"7102641544"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84952313223", "doi"=>"10.1371/journal.pone.0141171", "sgr"=>"84952313223", "isbn"=>"1932-6203", "pmid"=>"26544975", "issn"=>"19326203", "pui"=>"607426523"}, "id"=>"ea4c8c01-ebfe-3685-881e-562890ed7089", "abstract"=>"BACKGROUND: T cells regulate the adaptive immune response and have altered function in autoimmunity. Systemic Lupus Erythematosus (SLE) has great diversity of presentation and treatment response. Peripheral blood component gene expression affords an efficient platform to investigate SLE immune dysfunction and help guide diagnostic biomarker development for patient stratification.\\n\\nMETHODS: Gene expression in peripheral blood T cell samples for 14 SLE patients and 4 controls was analyzed by high depth sequencing. Unbiased clustering of genes and samples revealed novel patterns related to disease etiology. Functional annotation of these genes highlights pathways and protein domains involved in SLE manifestation.\\n\\nRESULTS: We found transcripts for hundreds of genes consistently altered in SLE T cell samples, for which DAVID analysis highlights induction of pathways related to mitochondria, nucleotide metabolism and DNA replication. Fewer genes had reduced mRNA expression, and these were linked to signaling, splicing and transcriptional activity. Gene signatures associated with the presence of dsDNA antibodies, low complement levels and nephritis were detected. T cell gene expression also indicates the presence of several patient subtypes, such as having only a minimal expression phenotype, male type, or severe with or without induction of genes related to membrane protein production.\\n\\nCONCLUSIONS: Unbiased transcriptome analysis of a peripheral blood component provides insight on autoimmune pathophysiology and patient variability. We present an open source workflow and richly annotated dataset to support investigation of T cell biology, develop biomarkers for patient stratification and perhaps help indicate a source of SLE immune dysfunction.", "link"=>"http://www.mendeley.com/research/t-cell-transcriptomes-describe-patient-subtypes-systemic-lupus-erythematosus", "reader_count"=>29, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Other"=>4, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Other"=>4, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>3, "Computer Science"=>2, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2415449"], "description"=>"<p>Genes were selected based on their ability to differentiate first all SLE samples from controls (top) and then subtypes A or B from the others. Although not all of the genes selected had statistically different expression from all other groups, their use in concert is expected to be sufficient for stratification. Error bars represent median absolute deviation from the median value for each group, and * signifies p<0.05 by Kruskal-Wallis rank-sum followed by Bonferroni-corrected Dunn post test.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596301, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g005", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Marker_gene_expression_suggested_to_identify_SLE_patient_subtypes_/1596301", "title"=>"Marker gene expression suggested to identify SLE patient subtypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415432"], "description"=>"<p><b>A)</b> Distribution of expression stratified at the 1.5-, 2-fold and q<0.05 CUFFDIFF2 significance levels. <b>B)</b> Relationship between q values and expression fold change in SLE relative to control. <b>C)</b> Select genes significantly increased or decreased as determined by sequencing and CUFFDIFF2, with those confirmed by DESeq2 in bold. <b>D)</b> Example constituent data for OAS2 and NR4A2 in control, inactive and active (SLEDAI >6) samples, where error bars represent the median absolute deviation about the median.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596297, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SLE_T_cells_display_more_genes_with_increased_rather_than_decreased_expression_/1596297", "title"=>"SLE T cells display more genes with increased rather than decreased expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415431"], "description"=>"<p><b>A)</b> Samples were obtained from peripheral blood by negative selection and mRNA was sequenced at high depth. CUFFLINKS generated per-sample expression values and CUFFDIFF2 and DESeq2 were used for groupwise comparisons, which were repeated following discovery of novel sample subgroups. <b>B)</b> Frequency of SLE symptom presentation at blood draw for patient samples. Highlighting colors based on patient subtypes determined by downstream analysis.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596296, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_cell_transcriptome_workflow_and_distribution_of_major_clinical_signs_in_the_SLE_patient_cohort_/1596296", "title"=>"T cell transcriptome workflow and distribution of major clinical signs in the SLE patient cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415460"], "description"=>"<p>The number of chromatin immunoprecipitation binding sites within a 3kb window about significantly induced genes were counted <b>A)</b> Factors binding near induced genes which themselves are induced. <b>B)</b> Factors binding near these genes having reduced mRNA. <b>C)</b> ChIP factors with unchanged mRNA and more than 100 binding sites near induced loci. <b>D)</b> Expression of select chromatin factors by sample type, where error bars represent the median absolute deviation from the median.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596303, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g007", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ENCODE_ChIP_analysis_identifies_factors_which_account_for_induced_expression_in_SLE_T_cells_/1596303", "title"=>"ENCODE ChIP analysis identifies factors which account for induced expression in SLE T cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415461"], "description"=>"<p>Increased dsDNA binding (dsDNA), low complement (C3 or C4) or nephritis (hematuria or proteinuria) were the major symptoms most prevalent. SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; PGA, Physician's global assessment; ESR, erythrocyte sedimentation rate; WBC, white blood cell; RBC, red blood cell; HPF, high-power field. Nephritis was confirmed by recent biopsy and patient L078 has minimal change disease deemed unrelated to lupus.</p><p>Clinical manifestations of the enrolled SLE patients.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596304, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_manifestations_of_the_enrolled_SLE_patients_/1596304", "title"=>"Clinical manifestations of the enrolled SLE patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415459"], "description"=>"<p>The number of genes with altered expression used for each query is in parentheses for each comparison. Significant terms with Benjamini q values <0.05 are in bold. More terms were detected for Control versus SLE samples by removal of male samples (CON v SLE(F)). Further refinement was obtained by grouping minor expression phenotype samples instead with controls (C+0+A(F) v B+C). Redundant and nonspecific terms were discarded and the remaining were ranked by the number of genes associated.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596302, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g006", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distinct_biological_pathways_and_protein_domains_are_identified_following_sample_clustering_/1596302", "title"=>"Distinct biological pathways and protein domains are identified following sample clustering.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415436"], "description"=>"<p><b>A)</b> Genes with altered expression in lupus T cells relative to controls, which also showed moderate variation across all samples, were median normalized and Pearson clustered with average linkage, where red and blue denote high and low expression. <b>B)</b> Removal of genes with expression outside of the top quartile permits identification of subtype signature genes. <b>C)</b> Unbiased NMF clustering using the same input genes yields similar patient subgroups. <b>D)</b> SVD clustering of samples provides an approximate metric of sample similarity, where average values for control, affected and all samples are centrally located.</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596299, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Unbiased_clustering_identifies_patient_subtypes_by_T_cell_gene_expression_/1596299", "title"=>"Unbiased clustering identifies patient subtypes by T cell gene expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415434"], "description"=>"<p>Select genes with differential expression in women largely unique to each symptom were detected by Mann-Whitney rank sum tests related to <b>A)</b> increased presence of dsDNA antibodies <b>B)</b> Low C3 or C4 complement levels or <b>C)</b> biopsy-confirmed lupus nephritis. Error bars represent median absolute deviation from the median value for each group and *p<0.05, **p<0.01 for pairwise tests conducted on samples from patients with or without each symptom (healthy control data plotted only for comparison).</p>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596298, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0141171.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_cell_expression_of_specific_genes_linked_to_major_clinical_manifestations_of_SLE_/1596298", "title"=>"T cell expression of specific genes linked to major clinical manifestations of SLE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 03:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/2415583", "https://ndownloader.figshare.com/files/2415584", "https://ndownloader.figshare.com/files/2415585", "https://ndownloader.figshare.com/files/2415586", "https://ndownloader.figshare.com/files/2415587", "https://ndownloader.figshare.com/files/2415588"], "description"=>"<div><p>Background</p><p>T cells regulate the adaptive immune response and have altered function in autoimmunity. Systemic Lupus Erythematosus (SLE) has great diversity of presentation and treatment response. Peripheral blood component gene expression affords an efficient platform to investigate SLE immune dysfunction and help guide diagnostic biomarker development for patient stratification.</p><p>Methods</p><p>Gene expression in peripheral blood T cell samples for 14 SLE patients and 4 controls was analyzed by high depth sequencing. Unbiased clustering of genes and samples revealed novel patterns related to disease etiology. Functional annotation of these genes highlights pathways and protein domains involved in SLE manifestation.</p><p>Results</p><p>We found transcripts for hundreds of genes consistently altered in SLE T cell samples, for which DAVID analysis highlights induction of pathways related to mitochondria, nucleotide metabolism and DNA replication. Fewer genes had reduced mRNA expression, and these were linked to signaling, splicing and transcriptional activity. Gene signatures associated with the presence of dsDNA antibodies, low complement levels and nephritis were detected. T cell gene expression also indicates the presence of several patient subtypes, such as having only a minimal expression phenotype, male type, or severe with or without induction of genes related to membrane protein production.</p><p>Conclusions</p><p>Unbiased transcriptome analysis of a peripheral blood component provides insight on autoimmune pathophysiology and patient variability. We present an open source workflow and richly annotated dataset to support investigation of T cell biology, develop biomarkers for patient stratification and perhaps help indicate a source of SLE immune dysfunction.</p></div>", "links"=>[], "tags"=>["membrane protein production.ConclusionsUnbiased transcriptome analysis", "depth sequencing", "T Cell Transcriptomes Describe Patient Subtypes", "complement levels", "patient stratification.MethodsGene expression", "4 controls", "14 SLE patients", "DAVID analysis", "patient subtypes", "mRNA expression", "nucleotide metabolism", "Protein domains", "gene signatures", "treatment response", "expression phenotype", "Systemic lupus erythematosus", "Peripheral blood component gene expression", "Functional annotation", "blood T cell samples", "disease etiology", "T cell biology", "support investigation", "source workflow", "patient stratification", "T cell gene expression", "dsDNA antibodies", "transcriptional activity", "DNA replication", "Systemic Lupus Erythematosus BackgroundT cells", "biomarker development", "SLE manifestation.ResultsWe", "patient variability", "novel patterns", "SLE T cell samples", "blood component"], "article_id"=>1596342, "categories"=>["Uncategorised"], "users"=>["Sean J. Bradley", "Abel Suárez-Fueyo", "David R. Moss", "Vasileios C. Kyttaris", "George C. Tsokos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0141171.s001", "https://dx.doi.org/10.1371/journal.pone.0141171.s002", "https://dx.doi.org/10.1371/journal.pone.0141171.s003", "https://dx.doi.org/10.1371/journal.pone.0141171.s004", "https://dx.doi.org/10.1371/journal.pone.0141171.s005", "https://dx.doi.org/10.1371/journal.pone.0141171.s006"], "stats"=>{"downloads"=>6, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_Cell_Transcriptomes_Describe_Patient_Subtypes_in_Systemic_Lupus_Erythematosus_/1596342", "title"=>"T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-11-06 03:13:57"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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