Pharmacogenomics in early-phase clinical development.

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs.

VizMaps: A Bayesian Topic Modeling Based PubMed Search Interface

A common challenge that users of academic databases face is making sense of their query outputs for knowledge discovery. This is exacerbated by the size and growth of modern databases. PubMed, a central index of biomedical literature, contains over 25 million citations, and can output search results containing hundreds of thousands of citations. Under these conditions, efficient knowledge discovery requires a different data structure than a chronological list of articles. It requires a method of conveying what the important ideas are, where they are located, and how they are connected; a method of allowing users to see the underlying topical structure of their search. This paper presents VizMaps, a PubMed search interface that addresses some of these problems. Given search terms, our main backend pipeline extracts relevant words from the title and abstract, and clusters them into discovered topics using Bayesian topic models, in particular the Latent Dirichlet Allocation (LDA). It then outputs a visual, navigable map of the query results.

Hyperspectral Image Classification with Nonlinear Methods

This thesis introduces two related lines of study on classification of hyperspectral images with nonlinear methods. First, it describes a quantitative and systematic evaluation, by the author, of each major component in a pipeline for classifying hyperspectral images (HSI) developed earlier in a joint collaboration [23]. The pipeline, with novel use of nonlinear classification methods, has reached beyond the state of the art in classification accuracy on commonly used benchmarking HSI data [6], [13]. More importantly, it provides a clutter map, with respect to a predetermined set of classes, toward the real application situations where the image pixels not necessarily fall into a predetermined set of classes to be identified, detected or classified with.

The particular components evaluated are a) band selection with band-wise entropy spread, b) feature transformation with spatial filters and spectral expansion with derivatives c) graph spectral transformation via locally linear embedding for dimension reduction, and d) statistical ensemble for clutter detection. The quantitative evaluation of the pipeline verifies that these components are indispensable to high-accuracy classification.

Secondly, the work extends the HSI classification pipeline with a single HSI data cube to multiple HSI data cubes. Each cube, with feature variation, is to be classified of multiple classes. The main challenge is deriving the cube-wise classification from pixel-wise classification. The thesis presents the initial attempt to circumvent it, and discuss the potential for further improvement.