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Purity Independent Subtyping of Tumors (PurIST), a clinically robust single sample classifier for tumor subtyping in pancreatic cancer (NanoString)

ABSTRACT: We assess three major subtype classification schemas in the context of results from two clinical trials and by meta-analysis of publicly available expression data to assess statistical criteria of subtype robustness and overall clinical relevance. We then developed a Single Sample Classifier (SSC) using penalized logistic regression based on the most robust and replicable schema. We demonstrate that a tumor-intrinsic two subtype schema is most robust, replicable, and clinically relevant. We developed purity independent subtyping of tumors (PurIST), a SSC with robust and highly replicable performance on a wide range of platforms and sample types. We show that PurIST subtypes have meaningful associations with patient prognosis and have significant implications for treatment response to FOLIFIRNOX. Keywords: Expression profiling by array

ORGANISM(S): Homo sapiens

PROVIDER: GSE131051 | GEO | 2020/02/21

REPOSITORIES: GEO

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Purity Independent Subtyping of Tumors (PurIST), a clinically robust single-sample classifier for tumor subtyping in pancreatic cancer (RNA-Seq)

Project description:Purpose: Molecular subtyping for pancreatic cancer has made substantial progress in recent years, facilitating the optimization of existing therapeutic approaches to improve clinical outcomes in pancreatic cancer. With advances in treatment combinations and choices, it is becoming increasingly important to determine ways to place patients on the best therapies upfront. Although various molecular subtyping systems for pancreatic cancer have been proposed, consensus regarding proposed subtypes, as well as their relative clinical utility, remains largely unknown and presents a natural barrier to wider clinical adoption. Methods: We assess three major subtype classification schemas in the context of results from two clinical trials and by meta-analysis of publicly available expression data to assess statistical criteria of subtype robustness and overall clinical relevance. We then developed a single-sample classifier (SSC) using penalized logistic regression based on the most robust and replicable schema. Results: We demonstrate that a tumor-intrinsic two-subtype schema is most robust, replicable, and clinically relevant. We developed Purity Independent Subtyping of Tumors (PurIST), a SSC with robust and highly replicable performance on a wide range of platforms and sample types. We show that PurIST subtypes have meaningful associations with patient prognosis and have significant implications for treatment response to FOLIFIRNOX. Conclusions: The flexibility and utility of PurIST on low-input samples such as tumor biopsies allows it to be used at the time of diagnosis to facilitate the choice of effective therapies for patients with pancreatic ductal adenocarcinoma and should be considered in the context of future clinical trials.

2019-12-10 | GSE131050 | GEO

Purity Independent Subtyping of Tumors (PurIST), a clinically robust single sample classifier for tumor subtyping in pancreatic cancer

Project description:Purity Independent Subtyping of Tumors (PurIST), a clinically robust single sample classifier for tumor subtyping in pancreatic cancer

| PRJNA607898 | ENA

Purity Independent Subtyping of Tumors (PurIST), a clinically robust single sample classifier for tumor subtyping in pancreatic cancer (NanoString)

Project description:Purity Independent Subtyping of Tumors (PurIST), a clinically robust single sample classifier for tumor subtyping in pancreatic cancer (NanoString)

| PRJNA607901 | ENA

Purity Independent Subtyping of Tumors (PurIST), a clinically robust single-sample classifier for tumor subtyping in pancreatic cancer (RNA-Seq)

Project description:Purity Independent Subtyping of Tumors (PurIST), a clinically robust single-sample classifier for tumor subtyping in pancreatic cancer (RNA-Seq)

| PRJNA542388 | ENA

Purity Independent Subtyping of Tumors (PurIST), A Clinically Robust, Single-sample Classifier for Tumor Subtyping in Pancreatic Cancer.

Project description:PurposeMolecular subtyping for pancreatic cancer has made substantial progress in recent years, facilitating the optimization of existing therapeutic approaches to improve clinical outcomes in pancreatic cancer. With advances in treatment combinations and choices, it is becoming increasingly important to determine ways to place patients on the best therapies upfront. Although various molecular subtyping systems for pancreatic cancer have been proposed, consensus regarding proposed subtypes, as well as their relative clinical utility, remains largely unknown and presents a natural barrier to wider clinical adoption.Experimental designWe assess three major subtype classification schemas in the context of results from two clinical trials and by meta-analysis of publicly available expression data to assess statistical criteria of subtype robustness and overall clinical relevance. We then developed a single-sample classifier (SSC) using penalized logistic regression based on the most robust and replicable schema.ResultsWe demonstrate that a tumor-intrinsic two-subtype schema is most robust, replicable, and clinically relevant. We developed Purity Independent Subtyping of Tumors (PurIST), a SSC with robust and highly replicable performance on a wide range of platforms and sample types. We show that PurIST subtypes have meaningful associations with patient prognosis and have significant implications for treatment response to FOLIFIRNOX.ConclusionsThe flexibility and utility of PurIST on low-input samples such as tumor biopsies allows it to be used at the time of diagnosis to facilitate the choice of effective therapies for patients with pancreatic ductal adenocarcinoma and should be considered in the context of future clinical trials.

| S-EPMC6942634 | biostudies-literature

Cerebrospinal fluid cell-free DNA methylomes subtyping pediatric medulloblastoma

Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from four subtypes of MB patients. We find highly concordance of DNA methylation between CSF ctDNA and tumor DNA in a subtype manner. Our results show that CSF ctNDA methylation can be a minimal invasive precisely method to assess epigenetic alterations of MB in a subtype manner, which is complementary to current diagnoses of MB tumors.

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Purity Independent Subtyping of Tumors (PurIST), a clinically robust single sample classifier for tumor subtyping in pancreatic cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-02-21 | GSE131049 | GEO

Spatially preserved multi-region transcriptomic subtyping and biomarkers of outcome with chemoimmunotherapy in extensive-stage small cell lung cancer [IMfirst_DSP cohort]

Project description:Transcriptomic subtyping holds promise for personalized therapy in extensive stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers associated with long-term chemoimmunotherapy benefit in human ES-SCLC. Our work highlights that high intratumoral heterogeneity, lack of consistent association with outcome, and unclear subtype-specific target expression are major challenges for SCLC subtype-based precision oncology. Pre-existing IFNϒ-driven immunity and mitochondrial metabolism seem key correlates of long-term efficacy for chemoimmunotherapy in ES-SCLC.

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Spatially preserved multi-region transcriptomic subtyping and biomarkers of outcome with chemoimmunotherapy in extensive-stage small cell lung cancer [CANTABRICO_DSP cohort]

2024-04-09 | GSE261345 | GEO

Prototypes for 4x44K PAM50 Subtyping

Project description:PAM50 intrinsic subtype classification (Parker JS, Mullins M, Cheang MCU, et al: Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes. J Clin Oncol 27:1160-1167, 2009) was used for the Z1031 patient cohort. However, to account for potential technical biases such as differences in platforms and laboratory protocols between the Z1031 data set and the PAM50 training set2, we normalized the Z1301 data set before applying the PAM50 algorithm. This is a critical step that must be taken into consideration for appropriate subtype predictions as our group and others have previously shown3,4. To appropriately normalize the Z1301 microarray data, which is entirely composed of ER-positive tumors, we needed to estimate technical bias from a cohort with equivalent subtype representation as the PAM50 training set. A set including ER-negative, HER2-positive and true normal breast samples were profiled under the same platform, protocol and laboratory (i.e. WashU) as the Z1301 data set. A total of 40 prototypic samples of the various molecular subtypes were selected to match the distribution in the PAM50 training set. The mean expression of each PAM50 gene was calculated in this set of 40. These values obtained from the prototypical sample set were used for calibration purposes and were included as a new WashU_4X44K_Calibration column in the CalibrationParameter file, which has been already provided in the PAM50 algorithm2. This adjustment step assures that each sample is placed in the appropriate ‘prototypic space’ by subtracting the calibration value of each PAM50 gene from the expression value of the corresponding gene in each tested sample. Finally, single sample predictions were performed in every Z1301 sample using the WashU_4X44K_Calibration parameter. The complete data set for the 40 prototypic arrays is submitted under GSE26082. 40 experiments were used as prototypical cases for subtype calibration purposes.

2011-05-10 | E-GEOD-26082 | biostudies-arrayexpress

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