Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations.

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Context:Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2–11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values.Objective:Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy.Design:Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19–84 yr) and 45 ACC patients (20–80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26–201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids.Results:Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers.Conclusions:Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.

We propose a new matrix learning scheme to extend relevance learning vector quantization (RLVQ), an efficient prototype-based classification algorithm, towards a general adaptive metric. By introducing a full matrix of relevance factors in the distance measure, correlations between different features and their importance for the classification scheme can be taken into account and automated, general metric adaptation takes place during training. In comparison to the weighted Euclidean metric used in RLVQ and its variations, a full matrix is more powerful to represent the internal structure of the data appropriately. Large margin generalization bounds can be transfered to this case leading to bounds which are independent of the input dimensionality. This also holds for local metrics attached to each prototype which corresponds to piecewise quadratic decision boundaries. The algorithm is tested in comparison to alternative LVQ schemes using an artificial data set, a benchmark multi-class problem from the UCI repository, and a problem from bioinformatics, the recognition of splice sites for C. elegans.

We describe and compare several post-correlation radio frequency interference classification methods. As data sizes of observations grow with new and improved telescopes, the need for completely automated, robust methods for radio frequency interference mitigation is pressing. We investigated several classification methods and find that, for the data sets we used, the most accurate among them is the SumThreshold method. This is a new method formed from a combination of existing techniques, including a new way of thresholding. This iterative method estimates the astronomical signal by carrying out a surface fit in the time-frequency plane. With a theoretical accuracy of 95% recognition and an approximately 0.1% false probability rate in simple simulated cases, the method is in practice as good as the human eye in finding RFI. In addition it is fast, robust, does not need a data model before it can be executed and works in almost all configurations with its default parameters. The method has been compared using simulated data with several other mitigation techniques, including one based upon the singular value decomposition of the time-frequency matrix, and has shown better results than the rest.Comment: 14 pages, 12 figures (11 in colour). The software that was used in the article can be downloaded from http://www.astro.rug.nl/rfi-software