Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies.

|We present an object recognition system based on the Dynamic Link Architecture, which is an extension to classical Arti cial Neural Networks. The Dynamic Link Architecture exploits correlations in the ne-scale temporal structure of cellular signals in order to group neurons dynamically into higher-order entities. These entities represent a v ery rich structure and can code for high level objects. In order to demonstrate the capabilities of the Dynamic Link Architecture we implemented a program that can recognize human faces and other objects from video images. Memorized objects are represented by sparse graphs, whose vertices are labeled by a multi-resolution description in terms of a local power spectrum, and whose edges are labeled by geometrical distance vectors. Object recognition can be formulated as elastic graph matching, which is performed here by stochastic optimization of a matching cost function. Our implementation on a transputer network successfully achieves recognition of human faces and o ce objects from gray level camera images. The performance of the program is evaluated by a statistical analysis of recognition results from a portrait gallery comprising images of 87 persons. Index Terms|Computer vision, distortion invariance, dynamic link architecture, elastic graph matching, object recognition, neural network, wavelet.

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Data clustering describes a set of frequently employed techniques in exploratory data analysis to extract "natural" group structure in data. Such groupings need to be validated to separate the signal in the data from spurious structure. In this context, finding an appropriate number of clusters is a particularly important model selection question. We introduce a measure of cluster stability to assess the validity of a cluster model. This stability measure quantifies the reproducibility of clustering solutions on a second sample, and it can be interpreted as a classification risk with regard to class labels produced by a clustering algorithm. The preferred number of clusters is determined by minimizing this classification risk as a function of the number of clusters. Convincing results are achieved on simulated as well as gene expression data sets. Comparisons to other methods demonstrate the competitive performance of our method and its suitability as a general validation tool for clustering solutions in real-world problems.

Comprehensive characterization of a proteome is a fundamental goal in proteomics. To achieve saturation coverage of a proteome or specific subproteome via tandem mass spectrometric identification of tryptic protein sample digests, proteomics data sets are growing dramatically in size and heterogeneity. The trend toward very large integrated data sets poses so far unsolved challenges to control the uncertainty of protein identifications going beyond well established confidence measures for peptide-spectrum matches. We present MAYU, a novel strategy that reliably estimates false discovery rates for protein identifications in large scale data sets. We validated and applied MAYU using various large proteomics data sets. The data show that the size of the data set has an important and previously underestimated impact on the reliability of protein identifications. We particularly found that protein false discovery rates are significantly elevated compared with those of peptide-spectrum matches. The function provided by MAYU is critical to control the quality of proteome data repositories and thereby to enhance any study relying on these data sources. The MAYU software is available as standalone software and also integrated into the Trans-Proteomic