BoBafit: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors’ profiles

Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, BoBafit, able to check and, eventually, to adjust the baseline region, according to both the tumor-specific alterations’ context and the sample-specific clustered genomic lesions. Several databases have been chosen to set up and validate the designed package, thus demonstrating the potential of BoBafit to adjust copy number (CN) data from different tumors and analysis techniques. Relevantly, the analysis highlighted that up to 25% of samples need a baseline region adjustment and a redefinition of CNAs calls, thus causing a change in the prognostic risk classification of the patients. We support the implementation of BoBafit within CN analysis bioinformatics pipelines to ensure a correct patient's stratification in risk categories, regardless of the tumor type

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways' genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells' differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells' phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future

Annual accumulation for Greenland updated using ice core data developed during 2000-2006 and analysis of daily coastal meteorological data

An updated accumulation map for Greenland is presented on the basis of 39 new ice core estimates of accumulation, 256 ice sheet estimates from ice cores and snow pits used in previous maps, and reanalysis of time series data from 20 coastal weather stations. The period 1950-2000 is better represented by the data than are earlier periods. Ice-sheetwide accumulation was estimated based on kriging. The average accumulation (95 confidence interval, or ±2 times standard error) over the Greenland ice sheet is 30.0 ± 2.4 g cm -2 a-1, with the average accumulation above 2000-m elevation being essentially the same, 29.9 ± 2.2 g cm-2 a -1. At higher elevations the new accumulation map maintains the main features shown in previous maps. However, there are five coastal areas with obvious differences: southwest, northwest, and eastern regions, where the accumulation values are 20-50 lower than previously estimated, and southeast and northeast regions, where the accumulation values are 20-50 higher than previously estimated. These differences are almost entirely due to new coastal data. The much lower accumulation in the southwest and the much higher accumulation in the southeast indicated by the current map mean that long-term mass balance in both catchments is closer to steady state than previously estimated. However, uncertainty in these areas remains high owing to strong gradients in precipitation from the coast inland. A significant and sustained precipitation measurement program will be needed to resolve this uncertainty. Copyright 2009 by the American Geophysical Union

Comparing satellite and helicopter-based methods for observing crevasses, application in East Antarctica

Knowing where crevasses are is critical for planning safe on-ice field operations. Previous methods have ranged from real-time imaging of subsurface structures using ground penetrating radar, to mapping of crevasses over large areas using satellite imagery, with each method having it\u27s own strengths and weaknesses. In this paper we compare the detection of crevasses at the Totten Glacier, East Antarctica, from helicopter-borne ground penetrating radar with satellite-based microwave synthetic aperture radar imagery. Our results show that the 80 MHz helicopter-borne ground penetrating radar was able to detect crevasses up to a depth of 70 m, with snow bridge thickness of \u3e30 m. Comparison with TerraSAR-X (X-band, 9.6 GHz) satellite imagery indicates that the latter is highly effective, detecting 100% of crevasses with snow bridges of up to 4m thick and detecting 95% of crevasses with snow bridges up to 10 m thick. The ability of both methods to identify individual crevasses is affected by several factors including crevasse geometry, survey or satellite orientation and snow moisture content, and further experiments are planned to investigate performance under a wider range of conditions

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val66Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes

Re-use of Agro-industrial Waste: Recovery of Valuable Compounds by Eco-friendly Techniques

The global demographic expansion has determined a voracious demand for edible goods, thus also originating the primary issues about the disposal of waste and by-products with high environmental impact. Waste, by-products and effluents coming from industrial processing and agricultural procedures of vegetables and fruit can be defined as biomass, according to CE directive 2001/77. Those raw materials are currently used as compost, animal feed and biofuel production. In addition, these products can be used as starting substrates for the production of high value-added compounds according to the biorefinery concept. In this review, the biorefinery strategy was applied on waste coming from the industrial processing of lemon and tomato, two of the most abundant vegetables in Italy

Cellular telephones: hazards or not?

Guidelines for limiting EM exposure provide protection against known adverse health effects. Biological effects, on the other hand, may or may not result in an adverse health effect. Main biological effects are reviewed: nervous system, cellular level, and molecular level. Some attention is given to devices affecting eye, ear, and heart. PW and ELF modulation are compared with CW fields. The influence of the near-field is discussed. There is a serious concern among the population in Europe about possible adverse biological effects due to GSM base stations. Quite surprisingly however, there is no concern about TV and FM exposure. The question of the "microwave syndrome" raises again. Low intensity exposure is discussed. Recommendations are analyzed in detail. Health issues are reviewed. Main references are given.Anglai