A user guide for the online exploration and visualization of PCAWG data.

The Pan-Cancer Analysis of Whole Genomes (PCAWG) project generated a vast amount of whole-genome cancer sequencing resource data. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we provide a user's guide to the five publicly available online data exploration and visualization tools introduced in the PCAWG marker paper. These tools are ICGC Data Portal, UCSC Xena, Chromothripsis Explorer, Expression Atlas, and PCAWG-Scout. We detail use cases and analyses for each tool, show how they incorporate outside resources from the larger genomics ecosystem, and demonstrate how the tools can be used together to understand the biology of cancers more deeply. Together, the tools enable researchers to query the complex genomic PCAWG data dynamically and integrate external information, enabling and enhancing interpretation.

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

The UCSC Cancer Genomics Browser: update 2015.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a web-based application that integrates relevant data, analysis and visualization, allowing users to easily discover and share their research observations. Users can explore the relationship between genomic alterations and phenotypes by visualizing various -omic data alongside clinical and phenotypic features, such as age, subtype classifications and genomic biomarkers. The Cancer Genomics Browser currently hosts 575 public datasets from genome-wide analyses of over 227,000 samples, including datasets from TCGA, CCLE, Connectivity Map and TARGET. Users can download and upload clinical data, generate Kaplan-Meier plots dynamically, export data directly to Galaxy for analysis, plus generate URL bookmarks of specific views of the data to share with others.

The Cancer Genomics Hub (CGHub): overcoming cancer through the power of torrential data.

The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. The CGHub currently contains >1.4 PB of data, has grown at an average rate of 50 TB a month and serves >100 TB per week. The architecture of CGHub is designed to support bulk searching and downloading through a Web-accessible application programming interface, enforce patient genome confidentiality in data storage and transmission and optimize for efficiency in access and transfer. In this article, we describe the design of these three components, present performance results for our transfer protocol, GeneTorrent, and finally report on the growth of the system in terms of data stored and transferred, including estimated limits on the current architecture. Our experienced-based estimates suggest that centralizing storage and computational resources is more efficient than wide distribution across many satellite labs. Database URL: https://cghub.ucsc.edu.

Effect of thermal treatment and frozen storage on lipid decomposition of light and dark muscles of saithe (Pollachius virens).

Lipid decomposition of saithe (Pollachius virens) light and dark muscles was monitored during frozen storage at -25°C of raw (up to 18 months) and cooked products. Samples were cooked after 0, 6 and 12 months raw storage then refrozen and stored at -25°C for 12 months to determine the stability of cooked-then-stored samples. Fatty acid profiles, formation of hydroperoxides (PV), thiobarbituric acid reactive substances (TBARS), fluorescence compounds (OFR) and free fatty acids (FFA) were evaluated throughout the storage for all samples. In general, results indicated that enzymatic lipolysis was the driving factor influencing the quality of saithe over raw storage and it mostly affected polyunsaturated lipids in the light muscle. Cooking, however, inhibited FFA formation and induced formation of PV and TBARS. This behavior was more evident in samples cooked after long raw storage periods. The initial quality of the raw material before cooking is therefore critical with regard to oxidative stability of cooked fish products.

Effects of temperature during frozen storage on lipid deterioration of saithe (Pollachius virens) and hoki (Macruronus novaezelandiae) muscles.

Lipid deterioration of two lean fish species, saithe (Pollachius virens) and hoki (Macruronus novaezelandiae), during frozen storage at -20 and -30°C (up to 18months) was studied. Lipid composition, lipid oxidation and hydrolysis, and sensory attributes were evaluated on both light and dark muscles of the fish species. Results showed significant lipid deterioration with extended storage time, but lower storage temperature showed significantly more preservative effects. A marked difference was observed between the composition of dark muscle of hoki and saithe. Polyunsaturated fatty acids were the predominant lipids in dark muscle of saithe, while monounsaturated fatty acids were predominant in dark muscle of hoki. Further, the hydrolytic activity differed greatly between dark muscle of hoki and saithe, with significantly lower activity observed in hoki. Present results indicate that both tertiary lipid oxidation and hydrolysis products are appropriate for assessing lipid deterioration of saithe and hoki light muscle during frozen storage.

Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) offers interactive visualization and exploration of TCGA genomic, phenotypic, and clinical data, as produced by the Cancer Genome Atlas Research Network. Researchers can explore the impact of genomic alterations on phenotypes by visualizing gene and protein expression, copy number, DNA methylation, somatic mutation and pathway inference data alongside clinical features, Pan-Cancer subtype classifications and genomic biomarkers. Integrated Kaplan-Meier survival analysis helps investigators to assess survival stratification by any of the information.

The UCSC Cancer Genomics Browser: update 2013.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a set of web-based tools to display, investigate and analyse cancer genomics data and its associated clinical information. The browser provides whole-genome to base-pair level views of several different types of genomics data, including some next-generation sequencing platforms. The ability to view multiple datasets together allows users to make comparisons across different data and cancer types. Biological pathways, collections of genes, genomic or clinical information can be used to sort, aggregate and zoom into a group of samples. We currently display an expanding set of data from various sources, including 201 datasets from 22 TCGA (The Cancer Genome Atlas) cancers as well as data from Cancer Cell Line Encyclopedia and Stand Up To Cancer. New features include a completely redesigned user interface with an interactive tutorial and updated documentation. We have also added data downloads, additional clinical heatmap features, and an updated Tumor Image Browser based on Google Maps. New security features allow authenticated users access to private datasets hosted by several different consortia through the public website.

Factors impacting the formation of monochloropropanediol (MCPD) fatty acid diesters during palm (Elaeis guineensis) oil production.

Recently, organic and inorganic chlorinated compounds were detected in crude and commercially refined palm oils. Further, the predominant formation mechanism of monochloropropanediol (MCPD) diesters at high temperatures (>170-180°C) was revealed. The present study involved the development and comparison of solutions to mitigate MCPD diester levels in oils from various stages of palm oil production. Partially refined palm oil samples and oil extracted from fresh palm fruits were submitted to bench-top deodorisation experiments. Application of glycerol and ethanol as refining aids during the deodorisation of refined-bleached palm oil proved to be moderately effective; about 25%-35% reduction of MCPD diester levels was achieved. Washing crude palm oil with ethanol-water (1:1) prior to deodorisation was also an effective strategy yielding an ∼30% reduction of MCPD diester contents. Washing palm fruit pulp before oil extraction, however, was most impactful, resulting in a 95% reduction of MCPD diesters when compared to the deodorised control oil. This suggests that intervention upstream in the process chain is most efficient in reducing levels of these contaminants in refined oils. Following the study, a root-cause analysis was performed in order to map the parameters potentially responsible for the occurrence of MCPD diesters in refined palm oil and related fractions.

Glycidyl esters in refined palm (Elaeis guineensis) oil and related fractions. Part II: practical recommendations for effective mitigation.

In a previous work, it was shown that at high temperatures (up to 280°C) glycidyl esters (GE) are formed from diacylglycerols (DAG) via elimination of free fatty acid (FFA). In the present study, the impact of DAG content and temperature on the formation of GE using a model vacuum system mimicking industrial edible oil deodorization is investigated. These deodorization experiments confirmed that the formation of GE from DAG is extensive at temperatures above 230-240°C, and therefore, this value should be considered as an upper limit for refining operations. Furthermore, experimental data suggest that the formation of GE accelerates in particular when the DAG levels in refined oils exceed 3-4% of total lipids. Analysis of the lipid composition of crude palm oil (CPO) samples allowed the estimation that this critical DAG content corresponds to about 1.9-2.5% of FFA, which is the conventional quality marker of CPO. Moreover, high levels (>100ppm) of GE were also found in palm fatty acid distillate samples, which may indicate that the level of GE in fully refined palm oils also depends on the elimination rate of GE into the fatty acid distillate.

Formation mechanisms of monochloropropanediol (MCPD) fatty acid diesters in refined palm (Elaeis guineensis) oil and related fractions.

Monochloropropanediol (MCPD) fatty acid esters are process contaminants generated during the deodorisation of edible oils. In particular, MCPD diesters are found in higher abundance in refined palm oil than other edible oils. In the present study, a series of model reactions mimicking palm oil deodorisation has been conducted with pure acylglycerols in the presence or absence of either organic or inorganic chlorine-containing compounds. Results showed that the bulk of MCPD diesters are formed above 200°C through the reaction of organochlorines with triacylglycerols (TAG). Additional experiments confirmed that this reaction can be initiated during palm oil deodorisation by hydrogen chloride (HCl) gas evolved through the thermal degradation of organochlorines present in the oil. Therein, the majority of the ultimately produced MCPD diesters are the result of HCl reacting with TAG, via protonation, followed by the elimination of a fatty acid residue. Two possible MCPD diester formation mechanisms are highlighted, both of which involve acyloxonium ion reactive intermediates. Investigations with pure TAG regio-isomers showed that MCPD ester formation is regioselective and the sn-1(3) position of the glycerol backbone is favoured.

The UCSC Cancer Genomics Browser: update 2011.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) comprises a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. The browser displays whole-genome views of genome-wide experimental measurements for multiple samples alongside their associated clinical information. Multiple data sets can be viewed simultaneously as coordinated 'heatmap tracks' to compare across studies or different data modalities. Users can order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways and user-contributed collections of genes. Integrated standard statistical tools provide dynamic quantitative analysis within all available data sets. The browser hosts a growing body of publicly available cancer genomics data from a variety of cancer types, including data generated from the Cancer Genome Atlas project. Multiple consortiums use the browser on confidential prepublication data enabled by private installations. Many new features have been added, including the hgMicroscope tumor image viewer, hgSignature for real-time genomic signature evaluation on any browser track, and 'PARADIGM' pathway tracks to display integrative pathway activities. The browser is integrated with the UCSC Genome Browser; thus inheriting and integrating the Genome Browser's rich set of human biology and genetics data that enhances the interpretability of the cancer genomics data.

Antioxidant properties of extracts obtained from raw, dry-roasted, and oil-roasted US peanuts of commercial importance.

Raw, skinless peanut kernels from US commercial production lines were dry- and oil-roasted according to standard industrial practices. Eighty percent (v/v) methanolic extracts from the peanut cultivars were prepared and characterized by RP-HPLC: five predominant compounds were found comprising free p-coumaric acid and potential p-coumaric acid derivatives, as elucidated by DAD-UV spectra with comparisons to those of commercial standards. A Spanish high-oleic peanut possessed the greatest naturally-occurring level of p-coumaric acid and its derivatives, followed by a high-oleic Runner, a normal Runner, and a Virginia peanut. Upon thermal processing, p-coumaric acid was liberated at the expense of its derivatives according to the relationship: oil roasting > dry roasting > raw. A high-oleic Runner exhibited the greatest increase (∼785%) in free p-coumaric acid levels after oil roasting. For many of the samples from the 2007 crop, processing increased the TPC and antioxidant capacities in the order of raw < dry roast < oil roast, but results were cultivar dependent. Oil-roasted peanuts were more effective at scavenging O2(.-) than their dry-roasted counterparts, as determined by a photochemiluminescence assay. Overall findings indicate that although thermal processing altered the composition of peanut kernel antioxidants, TPC values and radical-scavenging activities are preserved. Depending on peanut type, cultivar, and harvest date, enhanced antioxidant capacities can result.