CMR left ventricular strains beyond global longitudinal strain in differentiating light-chain cardiac amyloidosis from hypertrophic cardiomyopathy

BackgroundThe clinical value of left ventricular (LV) global longitudinal strain (GLS) in the differential diagnosis of light-chain cardiac amyloidosis (AL-CA) and hypertrophic cardiomyopathy (HCM) has been previously reported. In this study, we analyzed the potential clinical value of the LV long-axis strain (LAS) to discriminate AL-CA from HCM. Furthermore, we analyzed the association between all the LV global strain parameters derived from cardiac magnetic resonance (CMR) feature tracking and LAS in both the AL-CA and HCM patients to assess the differential diagnostic efficacies of these global peak systolic strains.Materials and methodsThus, this study enrolled 89 participants who underwent cardiac MRI (CMRI), consisting of 30 AL-CA patients, 30 HCM patients, and 29 healthy controls. The intra- and inter-observer reproducibility of the LV strain parameters including GLS, global circumferential strain (GCS), global radial strain (GRS), and LAS were assessed in all the groups and compared. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performances of the CMR strain parameters in discriminating AL-CA from HCM.ResultsThe intra- and inter-observer reproducibility of the LV global strains and LAS were excellent (range of interclass correlation coefficients: 0.907–0.965). ROC curve analyses showed that the differential diagnostic performances of the global strains in discriminating AL-CA from HCM were good to excellent (GRS, AUC = 0.921; GCS, AUC = 0.914; GLS, AUC = 0.832). Furthermore, among all the strain parameters analyzed, LAS showed the highest diagnostic efficacy in differentiating between AL-CA and HCM (AUC = 0.962).ConclusionCMRI-derived strain parameters such as GLS, LAS, GRS, and GCS are promising diagnostic indicators that distinguish AL-CA from HCM with high accuracy. LAS showed the highest diagnostic accuracy among all the strain parameters

Evolution of multiple cell clones over a 29-year period of a CLL patient

Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14−, 6q− and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death. Serial single-cell RNA sequencing reveals an expression pattern with high FOS, JUN and KLF4 at disease acceleration, which resolves following therapy, but reoccurs following relapse and death. Transcriptome evolution indicates complex changes in expression occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy

Full-length single-cell RNA-seq applied to a viral human cancer:applications to HPV expression and splicing analysis in HeLa S3 cells

Background: Viral infection causes multiple forms of human cancer, and HPV infection is the primary factor in cervical carcinomas Recent single-cell RNA-seq studies highlight the tumor heterogeneity present in most cancers, but virally induced tumors have not been studied HeLa is a well characterized HPV+ cervical cancer cell line Result: We developed a new high throughput platform to prepare single-cell RNA on a nanoliter scale based on a customized microwell chip Using this method, we successfully amplified full-length transcripts of 669 single HeLa S3 cells and 40 of them were randomly selected to perform single-cell RNA sequencing Based on these data, we obtained a comprehensive understanding of the heterogeneity of HeLa S3 cells in gene expression, alternative splicing and fusions Furthermore, we identified a high diversity of HPV-18 expression and splicing at the single-cell level By co-expression analysis we identified 283 E6, E7 co-regulated genes, including CDC25, PCNA, PLK4, BUB1B and IRF1 known to interact with HPV viral proteins Conclusion: Our results reveal the heterogeneity of a virus-infected cell line It not only provides a transcriptome characterization of HeLa S3 cells at the single cell level, but is a demonstration of the power of single cell RNA-seq analysis of virally infected cells and cancers

RNA-Seq Analyses Generate Comprehensive Transcriptomic Landscape and Reveal Complex Transcript Patterns in Hepatocellular Carcinoma

RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related hepatocellular carcinoma (HCC) has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from HCC patients on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify >50% of all the annotated genes for each sample. Furthermore, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism-related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3–24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene and exon levels, implying a much complex landscape of transcript-specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system-wide levels