In this paper, we describe the problem of recommending conference sessions to attendees and show how novel extensions to traditional model-based recommender systems, as suggested in Adomavicius and Tuzhilin [CHECK END OF SENTENCE], can address this problem. We introduce Recommendation Engine by CONjoint Decomposition of ITems and USers (RECONDITUS)-a technique that is an extension of preference-based recommender systems to recommend items from a new disjoint set to users from a new disjoint set. The assumption being that preferences exhibited by users with known usage behavior (e.g., past conference session attendance), which can be abstracted by projections of user and item matrices, will be similar to ones of new (different) users where the basic environment and item domain are the same (e.g., new conference). RECONDITUS requires no item ratings, but operates on observed user behavior such as past conference session attendance. The RECONDITUS paradigm consists of projections of both user and item data, and the learning of relationships in projected space. Once established, the relationships enable predicting new relationships and provide associated recommendations. The approach can encompass several traditional data mining problems where both clustering and prediction are necessary. RECONDITUS has been evaluated using data from the Oracle OpenWorld conference.

MOTIVATION: Well-annotated gene sets representing the universe of the biological processes are critical for meaningful and insightful interpretation of large-scale genomic data. The Molecular Signatures Database (MSigDB) is one of the most widely used repositories of such sets. RESULTS: We report the availability of a new version of the database, MSigDB 3.0, with over 6700 gene sets, a complete revision of the collection of canonical pathways and experimental signatures from publications, enhanced annotations and upgrades to the web site. AVAILABILITY AND IMPLEMENTATION: MSigDB is freely available for non-commercial use at http://www.broadinstitute.org/msigdb.

UNLABELLED: Gene Set Enrichment Analysis (GSEA) is a computational method that assesses whether an a priori defined set of genes shows statistically significant, concordant differences between two biological states. We report the availability of a new version of the Java based software (GSEA-P 2.0) that represents a major improvement on the previous release through the addition of a leading edge analysis component, seamless integration with the Molecular Signature Database (MSigDB) and an embedded browser that allows users to search for gene sets and map them to a variety of microarray platform formats. This functionality makes it possible for users to directly import gene sets from MSigDB for analysis with GSEA. We have also improved the visualizations in GSEA-P 2.0 and added links to a new form of concise gene set annotations called Gene Set Cards. These additions, as well as other improvements suggested by over 3500 users who have downloaded the software over the past year have been incorporated into this new release of the GSEA-P Java desktop program. AVAILABILITY: GSEA-P 2.0 is freely available for academic and commercial users and can be downloaded from http://www.broad.mit.edu/GSEA

BACKGROUND: Clustering analysis of microarray data is often criticized for giving ambiguous results because of sensitivity to data perturbation or clustering techniques used. In this paper, we describe a new method based on principal component analysis and ensemble consensus clustering that avoids these problems. RESULTS: We illustrate the method on a public microarray dataset from 36 breast cancer patients of whom 31 were diagnosed with at least two of three pathological stages of disease (atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Our method identifies an optimum set of genes and divides the samples into stable clusters which correlate with clinical classification into Luminal, Basal-like and Her2+ subtypes. Our analysis reveals a hierarchical portrait of breast cancer progression and identifies genes and pathways for each stage, grade and subtype. An intriguing observation is that the disease phenotype is distinguishable in ADH and progresses along distinct pathways for each subtype. The genetic signature for disease heterogeneity across subtypes is greater than the heterogeneity of progression from DCIS to IDC within a subtype, suggesting that the disease subtypes have distinct progression pathways. Our method identifies six disease subtype and one normal clusters. The first split separates the normal samples from the cancer samples. Next, the cancer cluster splits into low grade (pathological grades 1 and 2) and high grade (pathological grades 2 and 3) while the normal cluster is unchanged. Further, the low grade cluster splits into two subclusters and the high grade cluster into four. The final six disease clusters are mapped into one Luminal A, three Luminal B, one Basal-like and one Her2+. CONCLUSION: We confirm that the cancer phenotype can be identified in early stage because the genes altered in this stage progressively alter further as the disease progresses through DCIS into IDC. We identify six subtypes of disease which have distinct genetic signatures and remain separated in the clustering hierarchy. Our findings suggest that the heterogeneity of disease across subtypes is higher than the heterogeneity of the disease progression within a subtype, indicating that the subtypes are in fact distinct diseases.

SUMMARY: GeneCruiser is a web service allowing users to annotate their genomic data by mapping microarray feature identifiers to gene identifiers from databases, such as UniGene, while providing links to web resources, such as the UCSC Genome Browser. It relies on a regularly updated database that retrieves and indexes the mappings between microarray probes and genomic databases. Genes are identified using the Life Sciences Identifier standard. AVAILABILITY: GeneCruiser is freely available in the following forms: Web service and Web application, http://www.genecruiser.org; GenePattern, GeneCruiser access has been integrated into our microarray analysis platform, GenePattern. http://www.genepattern.org.

SUMMARY: GeneCluster 2.0 is a software package for analyzing gene expression and other bioarray data, giving users a variety of methods to build and evaluate class predictors, visualize marker lists, cluster data and validate results. GeneCluster 2.0 greatly expands the data analysis capabilities of GeneCluster 1.0 by adding classification, class discovery and permutation test methods. It includes algorithms for building and testing supervised models using weighted voting and k-nearest neighbor algorithms, a module for systematically finding and evaluating clustering via self-organizing maps, and modules for marker gene selection and heat map visualization that allow users to view and sort samples and genes by many criteria. GeneCluster 2.0 is a stand-alone Java application and runs on any platform that supports the Java Runtime Environment version 1.3.1 or greater. AVAILABILITY: http://www.broad.mit.edu/cancer/software

Classification of patient samples is a crucial aspect of cancer diagnosis and treatment. We present a method for classifying samples by computational analysis of gene expression data. We consider the classification problem in two parts: class discovery and class prediction. Class discovery refers to the process of dividing samples into reproducible classes that have similar behavior or properties, while class prediction places new samples into already known classes. We describe a method for performing class prediction and illustrate its strength by correctly classifying bone marrow and blood samples from acute leukemia patients. We also describe how to use our predictor to validate newly discovered classes, and we demonstrate how this technique could have discovered the key distinctions among leukemias if they were not already known. This proof-of-concept experiment paves the way for a wealth of future work on the molecular classification and understanding of disease.

We present timings and performance numbers for a new short range three dimensional (3D) molecular dynamics (MD) code, SPaSM, on the Connection Machine-5 (CM-5).We demonstrate that rurM with more than 108 particles are now possible on massively parallel MIMD computers.To the best of our knowledge this ti at least an opder of magnitade more particles than what has previously been reported.Typical production runs show sustained performance (including communication) in the range of 47-50 GFlops on a 1024 node CM-5 with vector units (VUS).The speed of the code scales linearly with the number of processors and with the number of particles and shows 95% parallel eficiency in the speedup.Passing Multi-Cell Molecular Dynamics on the Connection Machine 5, Parall.Comp. (1993) (in press).

We discuss different approaches to the short -range variab le-neighbor Molecular Dynamlcs problem on parallel mach ines and in particular the Connection Machzne CM-2. Tradltwnal Molecular Dynamics methods are reviewed and the computational require­ ments of parallel algorithms are analyzed. Three ap­ proaches based on parallel extensions of lznked lists, Verlet neighbor lzsts and coarse-grained cells are p­ resented and their advantages and disadvantages dis­ cussed. Performance evaluation and comparisons with other algorithms and machines are provided.