Lawrence H. Smith

A gene expression database for the molecular pharmacology of cancer.

We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.

The importance of the lexicon in tagging biological text

A part-of-speech tagger is a fundamental and indispensable tool in computational linguistics, typically employed at the critical early stages of processing. Although taggers are widely available that achieve high accuracy in very general domains, these do not perform nearly as well when applied to novel specialized domains, and this is especially true with biological text. We present a stochastic tagger that achieves over 97.44% accuracy on MEDLINE abstracts. A primary component of the tagger is its lexicon which enumerates the permitted parts-of-speech for the 10000 words most frequently occurring in MEDLINE. We present evidence for the conclusion that the lexicon is as vital to tagger accuracy as a training corpus, and more important than previously thought.

MedTag: A Collection of Biomedical Annotations

We present a database of annotated biomedical text corpora merged into a portable data structure with uniform conventions. MedTag combines three corpora, MedPost, ABGene and GENETAG, within a common relational database data model. The GENETAG corpus has been modified to reflect new definitions of genes and proteins. The MedPost corpus has been updated to include 1,000 additional sentences from the clinical medicine domain. All data have been updated with original MEDLINE text excerpts, PubMed identifiers, and tokenization independence to facilitate data accuracy, consistency and usability. The data are available in flat files along with software to facilitate loading the data into a relational SQL database from ftp://ftp.ncbi.nlm.nih.gov/pub/lsmith/MedTag/medtag.tar.gz.

On ordering free groups

The positive cones of the left orders on a free group can be described by their finite subsets. An algorithm is given for recognizing when a finite subset of a free group lies in a positive cone. This is used to show how one can construct a sequence of finite subsets of a positive cone whose union is the positive cone. Moreover, the method gives an overview of the positive cones of a free group. It is still an open problem whether there are positive cones which can be generated as a subsemigroup by a finite subset.

The value of parsing as feature generation for gene mention recognition

We measured the extent to which information surrounding a base noun phrase reflects the presence of a gene name, and evaluated seven different parsers in their ability to provide information for that purpose. Using the GENETAG corpus as a gold standard, we performed machine learning to recognize from its context when a base noun phrase contained a gene name. Starting with the best lexical features, we assessed the gain of adding dependency or dependency-like relations from a full sentence parse. Features derived from parsers improved performance in this partial gene mention recognition task by a small but statistically significant amount. There were virtually no differences between parsers in these experiments.

Analysis of gene expression data of the NCI 60 cancer cell lines using Bayesian hierarchical effects model

From the end of the last decade, NCI has been performing large screening of anticancer drug compounds and molecular targets on a pool of 60 cell lines of various types of cancer. In particular, a complete set of cDNA expression array data on the 60 cell lines are now available. To discover differentially-expressed genes in each type of cancer cell lines, we need to estimate a large number of genetic parameters, especially interaction effects for all combinations of cancer types and genes, by decomposing the total variance into biological and array instrumental components. This error decomposition is important to identify subtle genes with low biological variability. An innovative statistical method is required for simultaneously estimating more than 100,000 parameters of interaction effects and error components. We propose a Bayesian statistical approach based on the construction of a hierarchical model adopting parameterization of a liner effects model. The estimation of the model parameters is performed by Markov Chain Monte Carlo, a recent computer- intensive statistical resampling technique. We have identified novel genes whose effects have not been revealed by the previous clustering approaches to the gene expression data.

Corrigendum to: "On ordering free groups" [J. Symbolic Comput. 40 (2005) 1285-1290]

The maritime pump of present invention has a plurality of crutches and a floating block which keeps the maritime pump at the proper position in seawater. The crutches are set at the lateral sides of the pump body, which stabilize the pump body and make the pump body slide along with it. The density of the aforementioned floating block is lower than seawater and may be put on the top or the bottom of the pump body so that it keeps the pump body at the proper position of seawater. The pump body is a tube-shaped object and is attached with a hopper, to lead seawater into the pump body. The shape and size of the piston are the same as the area of the space of the tube-like pump body. The piston has guiding holes in the relative positions of the guiding sticks, so that the guiding sticks can penetrate the guiding holes and make the piston slide along with the guiding sticks to push seawater.