16190800
Pathway recognition and augmentation by computational analysis of microarray expression data
MOTIVATION
We present a system, QPACA (Quantitative Pathway Analysis in Cancer) for analysis of biological data in the context of pathways. QPACA supports data visualization and both fine- and coarse-grained specifications, but, more importantly, addresses the problems of pathway recognition and pathway augmentation.


RESULTS
Given a set of genes hypothesized to be part of a pathway or a coordinated process, QPACA is able to reliably distinguish true pathways from non-pathways using microarray expression data. Relying on the observation that only some of the experiments within a dataset are relevant to a specific biochemical pathway, QPACA automates selection of this subset using an optimization procedure. We present data on all human and yeast pathways found in the KEGG pathway database. In 117 out of 191 cases (61%), QPACA was able to correctly identify these positive cases as bona fide pathways with p-values measured using rigorous permutation analysis. Success in recognizing pathways was dependent on pathway size, with the largest quartile of pathways yielding 83% success. In cross-validation tests of pathway membership prediction, QPACA was able to yield enrichments for predicted pathway genes over random genes at rates of 2-fold or better the majority of the time, with rates of 10-fold or better 10-20% of the time.


AVAILABILITY
The software is available for academic research use free of charge by email request.


SUPPLEMENTARY INFORMATION
Data used in the paper may be downloaded from http://www.jainlab.org/downloads.html
5500839
Compass: A shape-based machine learning tool for drug design
SummaryBuilding predictive models for iterative drug design in the absence of a known target protein structure is an important challenge. We present a novel technique, Compass, that removes a major obstacle to accurate prediction by automatically selecting conformations and alignments of molecules without the benefit of a characterized active site. The technique combines explicit representation of molecular shape with neural network learning methods to produce highly predictive models, even across chemically distinct classes of molecules. We apply the method to predicting human perception of musk odor and show how the resulting models can provide graphical guidance for chemical modifications.
13422669
Incremental Parsing by Modular Recurrent Connectionist Networks
We present a novel, modular, recurrent connectionist network architecture which learns to robustly perform incremental parsing of complex sentences. From sequential input, one word at a time, our networks learn to do semantic role assignment, noun phrase attachment, and clause structure recognition for sentences with passive constructions and center embedded clauses. The networks make syntactic and semantic predictions at every point in time, and previous predictions are revised as expectations are affirmed or violated with the arrival of new information. Our networks induce their own "grammar rules" for dynamically transforming an input sequence of words into a syntactic/semantic interpretation. These networks generalize and display tolerance to input which has been corrupted in ways common in spoken language.
13887159
JANUS: Speech-to-Speech Translation Using Connectionist and Non-Connectionist Techniques
We present JANUS, a speech-to-speech translation system that utilizes diverse processing strategies, including connectionist learning, traditional AI knowledge representation approaches, dynamic programming, and stochastic techniques. JANUS translates continuously spoken English and German into German, English, and Japanese. JANUS currently achieves 87% translation fidelity from English speech and 97% from German speech. We present the JANUS system along with comparative evaluations of its interchangeable processing components, with special emphasis on the connectionist modules.
40224479
Morphological similarity: A 3D molecular similarity method correlated with protein-ligand recognition
Recognition of small molecules by proteins depends on three-dimensional molecular surface complementarity. However, the dominant techniques for analyzing the similarity of small molecules are based on two-dimensional chemical structure, with such techniques often outperforming three-dimensional techniques in side-by-side comparisons of correlation to biological activity. This paper introduces a new molecular similarity method, termed morphological similarity (MS), that addresses the apparent paradox. Two sets of molecule pairs are identified from a set of ligands whose protein-bound states are known crystallographically. Pairs that bind the same protein sites form the first set, and pairs that bind different sites form the second. MS is shown to separate the two sets significantly better than a benchmark 2D similarity technique. Further, MS agrees with crystallographic observation of bound ligand states, independent of information about bound states. MS is efficient to compute and can be practically applied to large libraries of compounds.
6517871
Deriving quantitative conclusions from microarray expression data
MOTIVATION
The last few years have seen the development of DNA microarray technology that allows simultaneous measurement of the expression levels of thousands of genes. While many methods have been developed to analyze such data, most have been visualization-based. Methods that yield quantitative conclusions have been diverse and complex.


RESULTS
We present two straightforward methods for identifying specific genes whose expression is linked with a phenotype or outcome variable as well as for systematically predicting sample class membership: (1) a conservative, permutation-based approach to identifying differentially expressed genes; (2) an augmentation of K-nearest-neighbor pattern classification. Our analyses replicate the quantitative conclusions of Golub et al. (1999; Science, 286, 531-537) on leukemia data, with better classification results, using far simpler methods. With the breast tumor data of Perou et al. (2000; Nature, 406, 747-752), the methods lend rigorous quantitative support to the conclusions of the original paper. In the case of the lymphoma data in Alizadeh et al. (2000; Nature, 403, 503-511), our analyses only partially support the conclusions of the original authors.


AVAILABILITY
The software and supplementary information are available freely to researchers at academic and non-profit institutions at http://cc.ucsf.edu/jain/public
34672891
Estimating Groundwater Pollution Source Location from Observed Breakthrough Curves Using Neural Networks
This paper presents the results of a study aimed at estimating groundwater pollution source location from observed breakthrough curves using neural networks. Two different methods of presenting the breakthrough curves to the ANN are investigated. The feed-forward multi-layer perceptron (MLP) type artificial neural network (ANN) models are employed. The ANNs were trained using the back-propagation training algorithm on simulated data. A new approach for ANN training using back-propagation is employed that considers two different error statistics to prevent over-training or under-training of the ANNs. The preliminary results indicate that the ANNs are very efficient tools for estimating the distance of the potential pollution source from the observation well where breakthrough curve is measured.
18557608
Performance Paradox : Information Technology Investments and Administrative Performance in the Case of the 50 U.S. State Governments
This study introduces the terminology of performance paradox in the context of IT (information technology) investment and use. Although it is somewhat related to the concept of productivity paradox, in the case of performance paradox, the dependent variable (i.e., the measure of performance) is not productivity, but some other measure of performance. This paper presents the results of a study that examined the relationship between IT investments by the 50 state governments of the United States and the administrative performance of these state governments. There are two parts to this study. In the first part, IT investments by state governments were related to multiple measures of state government performance, namely performance in financial management, human resource management, information technology management, capital management, and managing for results. In the second part of the study, IT investments by state governments were related to projected state government budget deficits. State budget deficits are used as a performance measure because they are an indicator of state government planning performance. Structural equation modeling was performed to analyze the data. The results indicate incidence of performance paradox. It appears as though the more U.S. state governments invest in IT, the worse they perform. However, there are also indications that with the passage of time, the relationship between IT investment and performance shows improvement. Thus, over time, the performance paradox becomes less pronounced. In some cases, it appears that past investments in IT actually help future performance.
8533646
Dimensionality reduction using genetic algorithms
Pattern recognition generally requires that objects be described in terms of a set of measurable features. The selection and quality of the features representing each pattern affect the success of subsequent classification. Feature extraction is the process of deriving new features from original features to reduce the cost of feature measurement, increase classifier efficiency, and allow higher accuracy. Many feature extraction techniques involve linear transformations of the original pattern vectors to new vectors of lower dimensionality. While this is useful for data visualization and classification efficiency, it does not necessarily reduce the number of features to be measured since each new feature may be a linear combination of all of the features in the original pattern vector. Here, we present a new approach to feature extraction in which feature selection and extraction and classifier training are performed simultaneously using a genetic algorithm. The genetic algorithm optimizes a feature weight vector used to scale the individual features in the original pattern vectors. A masking vector is also employed for simultaneous selection of a feature subset. We employ this technique in combination with the k nearest neighbor classification rule, and compare the results with classical feature selection and extraction techniques, including sequential floating forward feature selection, and linear discriminant analysis. We also present results for the identification of favorable water-binding sites on protein surfaces.
6932749
Adaptive stream resource management using Kalman Filters
To answer user queries efficiently, a stream management system must handle continuous, high-volume, possibly noisy, and time-varying data streams. One major research area in stream management seeks to allocate resources (such as network bandwidth and memory) to query plans, either to minimize resource usage under a precision requirement, or to maximize precision of results under resource constraints. To date, many solutions have been proposed; however, most solutions are ad hoc with hard-coded heuristics to generate query plans. In contrast, we perceive stream resource management as fundamentally a filtering problem, in which the objective is to filter out as much data as possible to conserve resources, provided that the precision standards can be met. We select the Kalman Filter as a general and adaptive filtering solution for conserving resources. The Kalman Filter has the ability to adapt to various stream characteristics, sensor noise, and time variance. Furthermore, we realize a significant performance boost by switching from traditional methods of caching static data (which can soon become stale) to our method of caching dynamic procedures that can predict data reliably at the server without the clients' involvement. In this work we focus on minimization of communication overhead for both synthetic and real-world streams. Through examples and empirical studies, we demonstrate the flexibility and effectiveness of using the Kalman Filter as a solution for managing trade-offs between precision of results and resources in satisfying stream queries.
39123560
High Quality Compression of Educational Videos Using Content-Adaptive Framework
With multimedia E-learning becoming popular, better compression algorithms are required that are space efficient but maintain the quality of video data, particularly slide and blackboard text. In this paper, an educational video compression technique is presented that dynamically allocates the space according to the content importance of each video segment in the educational videos. We present a phase correlation based motion estimation and compensation algorithm to encode important moving objects in efficient manner. Temporal coherence is exploited in a two phase manner. First, the frames with high similarity are categorized and encoded efficiently. Secondly, the compression ratio is adapted according to the frame content. The algorithm is compared with the state-of-the-art standards such as H.261, MPEG-4, etc. on large database. The comparison shows that for similar bit rates, the video quality for our algorithm is significantly better than the other methods.