Project description:RNA-seq of pre-treatment and post-relapse matched samples from melanoma patients RNA-seq was performed for matched samples before treatment and after relapse from six patients that have been treated with RAF or RAF+MEK inhibitors. Submitter declares that raw sequence data will be submitted to dbGaP due to patient privacy concerns.
Project description:We provide 5' and/or 3' single cell and single nuclei RNA sequencing data for matched comparisons of profiling from fresh (single cells) and frozen (single nuclei) samples of a non small cell lung cancer sample, a cutaneous melanoma sample , and a primary uveal melanoma sample. We also provide matched samples processed with published dissociation protocols (*TST and *CST) for two samples as comparison. Next, we profiled three sequential biopsies (one pre-treatment and two on-treatment) from the KEYNOTE-001 trial by 5' single-nuclei RNA sequencing from frozen specimens. For these three datapoints we provide matched SlideSeq V2 spatial transcriptomic data. Finally, we provide 5' single nuclei RNA-sequencing data for 7 liver-metastatic uveal melanoma samples profiled at pre, on, and post treatment timepoints with MEK-inhibitor selumetinib. For all samples profiled with 5' capture we also provide TCR receptor information. This study provides a framework for the application of single nuclei RNA-sequencing on clinical grade specimens, and demonstrates the feasibility of this approach to dissect the biology of archival specimens or rare diseases.
Project description:We provide 5' and/or 3' single cell and single nuclei RNA sequencing data for matched comparisons of profiling from fresh (single cells) and frozen (single nuclei) samples of a non small cell lung cancer sample, a cutaneous melanoma sample , and a primary uveal melanoma sample. We also provide matched samples processed with published dissociation protocols (*TST and *CST) for two samples as comparison. Next, we profiled three sequential biopsies (one pre-treatment and two on-treatment) from the KEYNOTE-001 trial by 5' single-nuclei RNA sequencing from frozen specimens. For these three datapoints we provide matched SlideSeq V2 spatial transcriptomic data. Finally, we provide 5' single nuclei RNA-sequencing data for 7 liver-metastatic uveal melanoma samples profiled at pre, on, and post treatment timepoints with MEK-inhibitor selumetinib. For all samples profiled with 5' capture we also provide TCR receptor information. This study provides a framework for the application of single nuclei RNA-sequencing on clinical grade specimens, and demonstrates the feasibility of this approach to dissect the biology of archival specimens or rare diseases.
Project description:Recent development of new therapies with immune checkpoint inhibitors (ICIs) and MAPK-inhibitors (MAPKis) have significantly improved the outcome in metastatic cutaneous melanoma (CM). However, therapy response is limited to subgroups of patients and clinically useful predictive biomarkers for treatment outcome are lacking. To discover treatment-related systemic changes in plasma and potential biomarkers associated with treatment outcomes, we analysed 45 plasma samples from 24 patients with metastatic (stage IV) CM, using HiRIEF LC-MS/MS, collected before (pre-trm) and during treatment (trm). Of these, 27 samples were taken from 15 metastatic CM patients treated with ICIs (13 pre-trm and 14 trm samples; 12 matched) and 9 patients treated with MAPKis (9 matched). Matched samples were trm and pre-trm samples taken from the same individual before treatment and after the first cycle of treatment (before the second cycle). We have analysed the change in the plasma protein levels during treatment by comparing the plasma levels in the trm samples to the pre-trm samples, to detect treatment-induced alterations in the plasma proteome. We have analysed the patients treated with ICIs separately from the patients treated with MAPKis, to detect treatment-specific changes for both.
Project description:We performed single-cell/nuclei RNA-sequencing (sc/snRNA-seq) of 22 treatment-naïve melanoma brain metastases (MBM; 5 samples using scRNA-seq and 17 snRNA-seq) from 21 patients and 10 treatment-naïve peripheral (extracranial) metastases (ECM; all snRNA-seq) from 10 patients. We performed matched spatial sequencing using SlideSeq2 (n=16) on 11 snRNA-seq samples.
Project description:In this report, we generated eight matched pairs of vemurafenib sensitive/resistant melanoma lines and subjected these to concurrent RNA-seq and H3K27Ac ChIP-seq analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27Ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on EMT and hypoxia-related pathways. We also observed significant and dynamic changes in super-enhancers that underpin these transcriptomic patterns. We subsequently verified the 2-class structure in pre-BRAFi and post-relapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAFi resistance.
Project description:In this report, we generated eight matched pairs of vemurafenib sensitive/resistant melanoma lines and subjected these to concurrent RNA-seq and H3K27Ac ChIP-seq analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27Ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on EMT and hypoxia-related pathways. We also observed significant and dynamic changes in super-enhancers that underpin these transcriptomic patterns. We subsequently verified the 2-class structure in pre-BRAFi and post-relapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAFi resistance.
Project description:1) Transcriptional profiles of highly purified (≥ 98%) PB CD8+ T-cells from newly diagnosed AML patients (pre-treatment) were compared to age-matched healthy controls and transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment and upon recovery following induction chemotherapy (paired samples). 2) Transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment (PRE) and upon recovery following induction chemotherapy (POST) (paired samples).
Project description:Transcriptional profiles of formalin-fixed-paraffin-embedded melanoma metastases including pre-treatment (PRE) and post-treatment (POST) specimens from 50 patients treated with BRAF inhibitors or with BRAF and MEK inhibitors