Sample Set Annotation Tool: A Common Peripheral Blood Gene-Set for Diagnosis and Prediction of Operational Tolerance in Pediatric and Adult Liver Transplantation

Study Design
Assay
Sample Info
Files
Info
Samples
Group Sets
Analysis

Purpose

The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation.

Hypothesis

Experimental Design

Two centers data was included, which are 41 samples from Stanford as the training set and 44 samples from UCLA as the test set. 26 samples from Stanford and 15 samples from UCLA were used in microarray Agilent whole human genome microarray

Experimental Variables

Controls

Methods

Agilent Feature Extraction Software was used for background subtraction GeneSpring was used for normalization

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi

Expected Samples:

41 Samples Loaded: 41

Species

Human (Homo sapiens)

Sample Source

Peripheral blood

Disease

Liver Transplant

Treatment Protocol

Growth Protocol

Extraction Protocol

The blood was drawn in the presence of sodium heparin. Total RNA was extracted using the RNeasy Mini Kit (Qiagen, Valencia, CA).

Storage Conditions

Sample Set Spreadsheet

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Samples Preview

Sample ID	!Sample_title	tissue	phenotype	sample type
GSM766080	Healthy Control 1	peripheral blood	control	10 human cell lines
GSM766081	Healthy Control 2	peripheral blood	control	10 human cell lines
GSM766082	Healthy Control 3	peripheral blood	control	10 human cell lines
GSM766083	Healthy Control 4	peripheral blood	control	10 human cell lines
GSM766084	Healthy Control 5	peripheral blood	control	10 human cell lines

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File

Samples Viewer / Editor

All fields are editable except the "Sample ID" column. To edit a cell, click within the cell. To edit a "date" cell, click on the calendar icon. To cancel an edit, press the ESC key.

Sample ID	!Sample Title	Tissue	Phenotype	Sample type
GSM766080	Healthy Control 1	peripheral blood	control	10 human cell lines
GSM766081	Healthy Control 2	peripheral blood	control	10 human cell lines
GSM766082	Healthy Control 3	peripheral blood	control	10 human cell lines
GSM766083	Healthy Control 4	peripheral blood	control	10 human cell lines
GSM766084	Healthy Control 5	peripheral blood	control	10 human cell lines
GSM766085	Healthy Control 6	peripheral blood	control	10 human cell lines
GSM766086	Stanford liver tolerance 3	peripheral blood	liver operational tolerance	10 human cell lines
GSM766087	Stanford liver tolerance 7	peripheral blood	liver operational tolerance	10 human cell lines
GSM766088	Stanford liver tolerance 8	peripheral blood	liver operational tolerance	10 human cell lines
GSM766089	Stanford liver tolerance 6	peripheral blood	liver operational tolerance	10 human cell lines
GSM766090	Stanford liver tolerance 5	peripheral blood	liver operational tolerance	10 human cell lines
GSM766091	Stanford liver tolerance 4	peripheral blood	liver operational tolerance	10 human cell lines
GSM766092	Stanford liver tolerance 2	peripheral blood	liver operational tolerance	10 human cell lines
GSM766093	Stanford liver non-tolerance 1	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766094	Stanford liver non-tolerance 12	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766095	Stanford liver non-tolerance 13	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766096	Stanford liver non-tolerance 2	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766097	Stanford liver non-tolerance 3	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766098	Stanford liver non-tolerance 4	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766099	Stanford liver non-tolerance 5	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766100	Stanford liver non-tolerance 7	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766101	Stanford liver non-tolerance 8	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766102	Stanford liver non-tolerance 9	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766103	Stanford liver non-tolerance 10	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766104	Stanford liver non-tolerance 11	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766105	Stanford liver non-tolerance 14	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766106	UCLA liver tolerance 1	peripheral blood	liver operational tolerance	10 human cell lines
GSM766107	UCLA liver tolerance 2	peripheral blood	liver operational tolerance	10 human cell lines
GSM766108	UCLA liver tolerance 3	peripheral blood	liver operational tolerance	10 human cell lines
GSM766109	UCLA liver tolerance 4	peripheral blood	liver operational tolerance	10 human cell lines
GSM766110	UCLA liver tolerance 9	peripheral blood	liver operational tolerance	10 human cell lines
GSM766111	UCLA liver tolerance 12	peripheral blood	liver operational tolerance	10 human cell lines
GSM766112	UCLA liver tolerance 22	peripheral blood	liver operational tolerance	10 human cell lines
GSM766113	UCLA liver tolerance 20	peripheral blood	liver operational tolerance	10 human cell lines
GSM766114	UCLA liver tolerance 21	peripheral blood	liver operational tolerance	10 human cell lines
GSM766115	UCLA liver non-tolerance 5	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766116	UCLA liver non-tolerance 6	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766117	UCLA liver non-tolerance 8	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766118	UCLA liver non-tolerance 10	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766119	UCLA liver non-tolerance 15	peripheral blood	liver operational non-tolerance	10 human cell lines
GSM766120	UCLA liver non-tolerance 17	peripheral blood	liver operational non-tolerance	10 human cell lines

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SIDRA