8551249
Functional census of mutation sequence spaces: the example of p53 cancer rescue mutants
Many biomedical problems relate to mutant functional properties across a sequence space of interest, e.g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 mutant rescue. We devised a general methodology for conducting a functional census of a mutation sequence space by choosing informative mutants early. The methodology was tested in a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of three (24 iterations). The first double-blind 15-point moving accuracy was 47 percent and the last was 86 percent; r = 0.01 before an epiphanic 16th iteration and r = 0.92 afterward. Useful mutants were chosen early (overall r = 0.80). Code and data are freely available (http://www.igb.uci.edu/research/research.html, corresponding authors: R.H.L. for computation and R.K.B. for biology)
12471299
Kernels for small molecules and the prediction of mutagenicity, toxicity and anti-cancer activity
MOTIVATION
Small molecules play a fundamental role in organic chemistry and biology. They can be used to probe biological systems and to discover new drugs and other useful compounds. As increasing numbers of large datasets of small molecules become available, it is necessary to develop computational methods that can deal with molecules of variable size and structure and predict their physical, chemical and biological properties.


RESULTS
Here we develop several new classes of kernels for small molecules using their 1D, 2D and 3D representations. In 1D, we consider string kernels based on SMILES strings. In 2D, we introduce several similarity kernels based on conventional or generalized fingerprints. Generalized fingerprints are derived by counting in different ways subpaths contained in the graph of bonds, using depth-first searches. In 3D, we consider similarity measures between histograms of pairwise distances between atom classes. These kernels can be computed efficiently and are applied to problems of classification and prediction of mutagenicity, toxicity and anti-cancer activity on three publicly available datasets. The results derived using cross-validation methods are state-of-the-art. Tradeoffs between various kernels are briefly discussed.


AVAILABILITY
Datasets available from http://www.igb.uci.edu/servers/servers.html
1954824
ChemDB: a public database of small molecules and related chemoinformatics resources
MOTIVATION
The development of chemoinformatics has been hampered by the lack of large, publicly available, comprehensive repositories of molecules, in particular of small molecules. Small molecules play a fundamental role in organic chemistry and biology. They can be used as combinatorial building blocks for chemical synthesis, as molecular probes in chemical genomics and systems biology, and for the screening and discovery of new drugs and other useful compounds.


RESULTS
We describe ChemDB, a public database of small molecules available on the Web. ChemDB is built using the digital catalogs of over a hundred vendors and other public sources and is annotated with information derived from these sources as well as from computational methods, such as predicted solubility and three-dimensional structure. It supports multiple molecular formats and is periodically updated, automatically whenever possible. The current version of the database contains approximately 4.1 million commercially available compounds and 8.2 million counting isomers. The database includes a user-friendly graphical interface, chemical reactions capabilities, as well as unique search capabilities.


AVAILABILITY
Database and datasets are available on http://cdb.ics.uci.edu.
2128704
Joint analysis of two microarray gene-expression data sets to select lung adenocarcinoma marker genes
BackgroundDue to the high cost and low reproducibility of many microarray experiments, it is not surprising to find a limited number of patient samples in each study, and very few common identified marker genes among different studies involving patients with the same disease. Therefore, it is of great interest and challenge to merge data sets from multiple studies to increase the sample size, which may in turn increase the power of statistical inferences. In this study, we combined two lung cancer studies using micorarray GeneChip®, employed two gene shaving methods and a two-step survival test to identify genes with expression patterns that can distinguish diseased from normal samples, and to indicate patient survival, respectively.ResultsIn addition to common data transformation and normalization procedures, we applied a distribution transformation method to integrate the two data sets. Gene shaving (GS) methods based on Random Forests (RF) and Fisher's Linear Discrimination (FLD) were then applied separately to the joint data set for cancer gene selection. The two methods discovered 13 and 10 marker genes (5 in common), respectively, with expression patterns differentiating diseased from normal samples. Among these marker genes, 8 and 7 were found to be cancer-related in other published reports. Furthermore, based on these marker genes, the classifiers we built from one data set predicted the other data set with more than 98% accuracy. Using the univariate Cox proportional hazard regression model, the expression patterns of 36 genes were found to be significantly correlated with patient survival (p < 0.05). Twenty-six of these 36 genes were reported as survival-related genes from the literature, including 7 known tumor-suppressor genes and 9 oncogenes. Additional principal component regression analysis further reduced the gene list from 36 to 16.ConclusionThis study provided a valuable method of integrating microarray data sets with different origins, and new methods of selecting a minimum number of marker genes to aid in cancer diagnosis. After careful data integration, the classification method developed from one data set can be applied to the other with high prediction accuracy.
43754145
Heaps with Bits
In this paper, we show how to improve the complexity of heap operations and heapsort using extra bits. We first study parallel complexity of implementing priority queue operations on a heap. While the insertion of a new element into a heap can be done as fast as parallel searching, we show how to delete the smallest element from a heap in constant time with a sublinear number of processors, and in sublogarithmic time with a sublogarithmic number of processors. The models of parallel computation used are the CREW PRAM and the CRCW PRAM. Our results improve those of previously known algorithms.
5002092
How to Train a Classifier Based on the Huge Face Database?
The development of web and digital camera nowadays has made it easier to collect more than hundreds of thousands of examples. How to train a face detector based on the collected enormous face database? This paper presents a manifold-based method to subsample. That is, we learn the manifold from the collected face database and then subsample training set by the estimated geodesic distance which is calculated during the manifold learning. Using the subsampled training set based on the manifold, we train an AdaBoost-based face detector. The trained detector is tested on the MIT+CMU frontal face test set. The experimental results show that the proposed method is effective and efficient to train a classifier confronted with the huge database.
27866706
A New Method of Circumscribing Beliefs: The Propositional Case
We propose here a new notion of a minimal model for forming circumscription in belief-logic by incorporating the notion of minimal models in the prepositional logic. This results in a new circumscription operation for belief-formulas than the one considered in [4-6]. An important feature of the new circumscription operation is its close relationship with the circumscription of prepositional formulas. For instance, we have CIRC[Bp] = B(CIRC[p]), where p is a prepositional formula. We give several examples to show that the new notion of circumscription fits quite well with intuition.
7817604
Topological-based classification using artificial gene networks
The topological properties of artificial gene networks that rely on the assessment of similarities between the expressions profile of gene pairs would be consistent with specific cellular states. Furthermore, some topological properties of the network would have significant variance regarding different cellular states. In this study, we proposed a novel and highly efficient computational framework for a topological-based classification using microarray gene expression data. Owing to the high prediction accuracy with this approach, we believe that there is a noticeable advantage of using topological-based classification. We used the microarray gene expression data sets containing 14 classes of cancer to construct 14 basic artificial gene networks accordingly. For each test sample, we add the sample into the data set of each class and reconstruct all of the networks. Cancer type was classified according to the correlation of topological quantity between the basic artificial gene networks and the reconstructed networks. Total classification accuracy can achieve 78.26% in the test data set (95.83% in the standard data set). After screening the quality of the standard data set, we can achieve a prediction accuracy of 86.48% in the test data set. Thus, we can achieve higher prediction accuracy in comparison to previous studies.