Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

Statistical and integrative system-level analysis of DNA methylation data

Epigenetics plays a key role in cellular development and function. Alterations to the epigenome are thought to capture and mediate the effects of genetic and environmental risk factors on complex disease. Currently, DNA methylation is the only epigenetic mark that can be measured reliably and genome-wide in large numbers of samples. This Review discusses some of the key statistical challenges and algorithms associated with drawing inferences from DNA methylation data, including cell-type heterogeneity, feature selection, reverse causation and system-level analyses that require integration with other data types such as gene expression, genotype, transcription factor binding and other epigenetic information

Effect of orange sweet potato (Ipomoea batatas) flour on the physical properties of fried extruded fish crackers

The effects of orange sweet potato flour addition to tapioca starch on the expansion, oil absorption, bulk density, water absorption index (WAI), water solubility index (WSI), hardness and colour of fried extruded fish crackers were investigated. The microstructure properties were assessed by Field Emission Scanning Electron Microscope (FESEM) and the sensory properties of fried extruded fish crackers were determined by quantitative descriptive analysis method. The shape and texture of the product were similar to that of normal breakfast cereal. Light brownish and slightly harder texture was obtained with addition of orange sweet potato flour to tapioca starch in the fried extruded fish crackers. The bulk density and water solubility index (WSI) increased with the increase in orange sweet potato flour addition. However, water absorption index (WAI), linear expansion, expansion ratio, volume expansion and oil absorption decreased as the amount of orange sweet potato increased. The microstructure studies revealed that fried extruded fish crackers with high percentage of orange sweet potato flour had small air cells and thick cell wall. The fried extruded fish crackers with 30% fish, 14% orange sweet potato flour and 56% tapioca starch had high crispiness score and accepted by the trained panellists.</p