Improving outcomes in multiple myeloma will not only involve development of new therapies, but better use of existing treatments. We performed RNA sequencing (RNA-Seq) on samples from newly diagnosed patients enrolled into the phase II PADIMAC study. Using an empirical Bayes approach and synthetic annealing, we developed and trained a seven-gene signature to predict treatment outcome. We tested the signature on independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass dataset, patients who were treated correctly according to the signature had a better progression-free and overall survival than those who were not. Indeed, the outcome for these correctly treated patients was non-inferior to those treated with combined bortezomib, lenalidomide, and dexamethasone (VRD). PADIMAC: Bortezomib, Adriamycin and Dexamethasone (PAD) therapy for previously untreated patients with multiple myeloma: Impact of minimal residual disease (MRD) in patients with deferred ASCT (autologous stem cell transplant) Overall design: RNA-Seq data from 44 patients enrolled into the PADIMAC study who provided RNA with an RNA Integrity score of 6 or greater. Thirteen out of forty-four patients had at least a very good partial remission sustained for at least a year without progression and were labelled as "bortezomib-good".
RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature.
Age, Specimen part, Subject
View SamplesLamin A/C was ablated in pancreatic acinar cells using Elastase1 driven, Cre-ErT mediated, LoxP recombination, causing excision of exons 10 and 11 of the Lmna gene
Lamin A/C Maintains Exocrine Pancreas Homeostasis by Regulating Stability of RB and Activity of E2F.
Sex
View SamplesLeptospirosis is a neglected zoonotic disease of global importance. Despite its prevalence, pathogenesis is still poorly understood. Our aim was to discover transcripts responsable for pathogenicity of leptospirosis. We compared the transcriptome profiles of saprophyte, attenuated and virulent strain of Leptospira spp.
Transcriptome datasets of macrophages infected with different strains of <i>Leptospira</i> spp.
Cell line
View SamplesSeptic shock is the most severe complication of sepsis, associated with high mortality. The patient's response to supportive therapy is very heterogeneous and the underlying mechanisms are still elusive. In order to identify which are the actors (genes and pathways) that play a role in establishing the response, we investigate the whole blood transcriptome in septic shock patients with positive and negative responses to early supportive hemodynamic therapy, assessed by changes in SOFA scores within the first 48 hours from ICU admission. We pinpointed genes and pathways that are differently modulated and enriched respectively within 48hrs between responders and non-responders. Overall design: We analyzed 31 patients (17 Responders and 14 Not Responders to early therapy). For each patient, 2 samples were collected. In particular the first sample (T1) collected within 16 hours from ICU admission whereas the second (T2) collected within 48 hours from ICU admission. Experimental groups (Responders and Not Responders) are defined accordingly with SOFA scores improvements within 48 hours.
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy.
Specimen part, Subject, Time
View SamplesBackground: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data and validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity, classic dengue fever or dengue hemorrhagic fever (DHF) and compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection
Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RUNX1, a transcription factor mutated in breast cancer, controls the fate of ER-positive mammary luminal cells.
Sex, Specimen part
View SamplesThe purpose of this microarray experiment was to obtain reference gene expression patterns of a number of epithelial cell populations [mammary stem cells (MASC), luminal progenitors (LP), alveolar luminal stem/progenitor cells (WC virgin-these are mammary epithelial cells genetically marked by Wap-Cre in virgin females), mature luminal cells (ML, mainly represent ductal luminal cells in virgin females), and alveolar luminal cells (WC preg these are alveolar cells genetically marked by Wap-Cre during mid-gestation)] present in the mammary gland of wildtype adult mice on a C57BL6 genetic background.
RUNX1, a transcription factor mutated in breast cancer, controls the fate of ER-positive mammary luminal cells.
Sex, Specimen part
View SamplesRUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and activates Foxa1, a key mature luminal TF gene involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss.
RUNX1, a transcription factor mutated in breast cancer, controls the fate of ER-positive mammary luminal cells.
Sex, Specimen part
View SamplesMicroRNA microarrays and RNA expression arrays were used to identify functional signaling between neural stem cell progenitor cells (NSPC) and brain endothelial cells (EC) that are critical during embryonic development and tissue repair following brain injury.
The role of microRNAs in neural stem cell-supported endothelial morphogenesis.
Specimen part, Disease, Treatment
View SamplesThe objective of this study was to obtain expression profiles of proliferative T-HEp3-GFP and dormant D-HEp3-GFP cells after one week in vivo. The second objective was find tumor cells quiescence associated genes in dormant D-HEp3 cells that are only quiescent when injected in vivo. In this case we compared cells one week growing vs. dormant for the indicated cells in chick embryo CAMs. After one week 5 embryos per cell line carrying the indicated cells were isolated, tumors collagenased as described below and sorted for GFP-high cells usig a MoFlo machine. The sorted cells > 5x10^4 were used to extract RNA and the pure RNA was used to perform expression profiling using the Affymetrix HG-u133plus2 arrays. Because of the low amount of D-HEp3 (dormant) cells recovered all tumor cells from the dormant nodules were pooled. The same was done for proliferative-sorted T-HEp3-GFP cells to allow comparisons. Arrays were performed in triplicate.
NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes.
Specimen part
View Samples