Peripheral blood transcriptomic profiles of kidney allograft pathology: biological pathways, comparison with biopsy signals and cellular origin
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Homo sapiens
SUBMITTER: Baptiste Lamarthée
PROVIDER: E-MTAB-11450 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To further explore the transcriptional changes in the kidney transplant biopsy at time of rejection, scRNAseq analysis was performed on 16 kidney transplant biopsy-derived cells using 10X Genomic technology.
2023-05-22 | E-MTAB-12051 | biostudies-arrayexpress
Project description:Molecular phenotyping of biopsies affords opportunities for increased precision and improved disease classification to address the limitations of conventional histologic diagnostic systems. We applied archetypal analysis, an unsupervised method similar to cluster analysis, to microarray data from 1208 prospectively collected kidney transplant biopsies from 13 centers. Seven machine learning-generated cross-validated classifier scores per biopsy were used as input for the archetypal analysis. Six archetypes representing extreme phenotypes were generated: no rejection; T cell-mediated rejection (TCMR); three phenotypes associated with antibody-mediated rejection (ABMR) - early-stage, fully-developed, and late-stage; and mixed rejection (TCMR plus early-stage ABMR). Each biopsy was assigned six scores, one for each archetype, that together represent a probabilistic assessment of that biopsy based on its rejection-related molecular properties. Viewed as clusters, the archetypes were similar to existing histologic Banff categories, but there was 32% disagreement, much of it probably reflecting the “noise” in the current histologic assessment system. Graft survival was worst for fully-developed and late-stage ABMR and was better predicted by molecular archetype scores than histologic diagnoses. The results provide a system for precision molecular assessment of biopsies and a new standard for recalibrating conventional diagnostic systems. (ClinicalTrials.gov NTC1299168) We applied archetypal analysis, an unsupervised method similar to cluster analysis, to microarray data from 1208 prospectively collected kidney transplant biopsies from 13 centers. This dataset is part of the TransQST collection.
2017-07-10 | E-GEOD-98320 | biostudies-arrayexpress
Project description:Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL and REN. Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the Molecular Microscope Diagnostic System. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had <50% cortex. Molecular scores for ABMR, TCMR, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection, and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex. We studied 26 pairs of cortex/medulla biopsies from 26 patients (4 unpaired), characterizing the clinical and histological features, and defined the mRNA phenotype with Affymetrix expression microarrays. We also studied 37 pairs of biopsies from biological replicates and 12 pairs from technical replicates. This dataset is part of the TransQST collection.
2017-04-27 | E-GEOD-95611 | biostudies-arrayexpress
Project description:ANCA-associated glomerulonephritis (AGN) associates with a high risk of end-stage kidneydisease. The role of kidney immune cells in local inflammation remains unclear. Herewe investigate kidney immune cell diversity and function. Kidney tissue from AGN patients (n=5) and a lupus nephritis (LN) patient (n=1) were aquired during a biopsy procedure for a clinical indication. Needle-core biopsies were obtained for histopathological examination, and an additional pass was performed to retrieve kidney tissue for scRNA-seq. Healthy kidney tissue (n=1) was obtained from a kidney that was surgically removed do tue due to a (non-invasive) papillary urothelial carcinoma. Immediately after collection, kidney tissue was processed into a single-cell suspension and sorted using a 4-color flow cytometry panel to isolate living, CD45+immune cells. To aid in the multi-omic characterization, surface markers and T and B cell repertoires were sequenced in 2 samples (1 AGN patient and the nephrectomy control). These samples were incubated with an oligo-antibody TotalSeq-C cocktail containing 130 unique cell surface antigens.
2024-06-28 | E-MTAB-13596 | biostudies-arrayexpress
Project description:We profile single cells from patients with colorectum cancer using Chromium 3’ and 5’ single-cell RNA-sequencing. Patients EXT001, EXT009, and EXT012 from the KUL dataset were first analyzed by Lee et al., 2020, and the raw data are available in ArrayExpress under the accession codes E-MTAB-8410 and E-MTAB-8107. Patients EXT018, EXT048, EXT113, and EXT121 from KUL dataset were previously analyzed by Joanito et al., 2022. The raw data of those patients are available in EGA under the accession codes EGAD00001008584 and EGAD00001008585.
2022-09-16 | E-MTAB-9934 | biostudies-arrayexpress
Project description:Histologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms. Antibody-mediated rejection is a major cause of kidney transplant failure, but the current diagnostic system misses most cases due to dependency on subjective non-standardized tests. We hypothesized that molecular features could provide a test to address this problem. We classified 403 biopsies by a reference standard based on microcirculation lesions and donor-specific HLA antibody, and used microarray analysis to develop a classifier that assigned each biopsy a score reflecting the probability of antibody-mediated rejection. The scores correlated with donor-specific antibody and histologic lesions: 42/45 biopsies with antibody-mediated rejection scores >0.5 had both donor-specific antibody and microcirculation lesions. Intermediate scores (0.2-0.5) were more ambiguous, but became more specific combined with donor-specific antibody. Compared to diagnoses based on histology-plus-donor-specific antibody, the scores had sensitivity 0.67; specificity 0.90. Donor-specific antibody improved the specificity to 0.97. The score correlated not only with diagnoses of individual pathologists but with the consensus among multiple pathologists. The classifier used transcripts expressed in endothelial cells (e.g. CDH13, DARC, ROBO4) and NK cells (e.g. CX3CR1, FGFBP2), as well as IFNG-inducible transcripts e.g. CXCL11. Thus the molecular phenotype of antibody-mediated rejection provides not only an objective test that predicts microcirculation lesions and donor-specific HLA antibody, but also offers mechanistic insights. All consenting renal transplant patients undergoing biopsies for cause as standard of care. 403 samples and 8 controls (nephrectomies). This dataset is part of the TransQST collection.
2013-02-13 | E-GEOD-36059 | biostudies-arrayexpress
Project description:The enigmatic natural killer (NK) cells mediate spontaneous cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity via cell surface Fc receptors. The dual functionality of NK cells may enable their participation in chronic active antibody-mediated rejection (CA-ABMR), wherein evidence for complement activation is inconsistent. We RNA sequenced 57 human kidney allograft biopsies to determine whether NK cell cytotoxicity pathway gene set enrichment is an attribute of CA-ABMR. Among the 15,910 intragraft-expressed genes, 60 were uniquely overexpressed in CA-ABMR compared to active antibody-mediated rejection (active-ABMR) or acute T cell-mediated rejection (TCMR), versus no rejection (NR) biopsies. Cell type annotation showed enrichment for T cells and NK cells, and molecular pathways related to T cells and NK cells in CA-ABMR versus active-ABMR biopsies. NK cell cytotoxicity gene set enrichment in CA-ABMR than in ABMR biopsies, but not in TCMR, was confirmed by gene set variation analysis. Cellular deconvolution analysis divulged a higher proportion of NK cells in CA-ABMR compared to active-ABMR, but not in TCMR; immunohistochemistry of 138 consecutive clinically indicated allograft biopsies validated a higher proportion of CD56+ NK cells in CA-ABMR. Principal component analysis of deconvolved immune cell transcriptomes separated CA-ABMR and TCMR from active-ABMR and NR biopsies. NK cell cytotoxicity pathway gene set was found to be enriched in rejection compared to no rejection biopsies in two publicly available kidney allograft microarray datasets. Altogether, CA-ABMR is exemplified by the overexpression of the NK cell pathway, and, surprisingly, compared to active-ABMR, is exemplified by key gene sets that are similar to TCMR.
2024-02-14 | GSE232825 | GEO
Project description:Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower eGFR, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR respectively diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.
2024-09-04 | GSE275126 | GEO
Project description:We compared the transcriptomic profile between patients without donor-specific antibodies (DSA-), patients with donor-specific antibodies without antibody-mediated rejection (DSA+ ABMR-) and patients with donor-specific antibodies and antibody-mediated rejection (DSA+ ABMR+). We found that patients with DSA+ ABMR+ had a distinct transcriptomic profile compared to DSA- and DSA+ ABMR- patients, characterized by upregulation of genes related to B cell activation and B cell effector functions.
2021-07-14 | GSE155670 | GEO
Project description:We compared the transcriptomic profile between patients without donor-specific HLA antibodies (DSA-), patients with donor-specific HLA antibodies without antibody-mediated rejection (DSA+ ABMR-) and patients with donor-specific HLA antibodies and antibody-mediated rejection (DSA+ ABMR+). We found that patient with DSA+ ABMR+ had a distinct transcriptomic profile compared to DSA- and DSA+ ABMR-, characterized by upregulation of genes encoding for germinal center T follicular helper cells function, T-B cell interaction and costimulatory molecules.
2021-07-01 | GSE134477 | GEO