Type inference for action semantics

Action semantics, developed by Mosses and Watt, is a metalanguage for denotational semantics in which program denotations are actions. We study actions as polymorphic combinators that operate on collections of types. Our work includes a category-sorted algebra-based model for action semantics; a unification-based type inference algorithm for action expressions similar to that used for ML, extended with subtypes and records; proofs of its soundness and completeness with respect to the model; and an algorithm for simplifying inheritance subtyping constraints on records to constraints on non-record primitives. Our work extends other research on type inference with subtypes and records, primarily because our results are based on a semantic model: we avoid the large constraint sets encountered by previous researchers because coercions are not needed in our model. Our system provides record concatenation and union operations, without the need for complex constraints on record types

A new statistical solution to the generality problem

The Generality Problem is widely recognized to be a serious problem for reliabilist theories of justification. James R. Beebe's Statistical Solution is one of only a handful of attempted solutions that has garnered serious attention in the literature. In their recent response to Beebe, Julien Dutant and Erik J. Olsson successfully refute Beebe's Statistical Solution. This paper presents a New Statistical Solution that countenances Dutant and Olsson's objections, dodges the serious problems that trouble rival solutions, and retains the theoretical virtues that made Beebe's solution so attractive in the first place. There indeed exists a principled, rigorous, conceptually sparse, and plausible solution to the Generality Problem: it is the New Statistical Solution

Parametric inference of recombination in HIV genomes

Recombination is an important event in the evolution of HIV. It affects the global spread of the pandemic as well as evolutionary escape from host immune response and from drug therapy within single patients. Comprehensive computational methods are needed for detecting recombinant sequences in large databases, and for inferring the parental sequences. We present a hidden Markov model to annotate a query sequence as a recombinant of a given set of aligned sequences. Parametric inference is used to determine all optimal annotations for all parameters of the model. We show that the inferred annotations recover most features of established hand-curated annotations. Thus, parametric analysis of the hidden Markov model is feasible for HIV full-length genomes, and it improves the detection and annotation of recombinant forms. All computational results, reference alignments, and C++ source code are available at http://bio.math.berkeley.edu/recombination/.Comment: 20 pages, 5 figure

Bayesian Inference for Latent Biologic Structure with Determinantal Point Processes (DPP)

We discuss the use of the determinantal point process (DPP) as a prior for latent structure in biomedical applications, where inference often centers on the interpretation of latent features as biologically or clinically meaningful structure. Typical examples include mixture models, when the terms of the mixture are meant to represent clinically meaningful subpopulations (of patients, genes, etc.). Another class of examples are feature allocation models. We propose the DPP prior as a repulsive prior on latent mixture components in the first example, and as prior on feature-specific parameters in the second case. We argue that the DPP is in general an attractive prior model for latent structure when biologically relevant interpretation of such structure is desired. We illustrate the advantages of DPP prior in three case studies, including inference in mixture models for magnetic resonance images (MRI) and for protein expression, and a feature allocation model for gene expression using data from The Cancer Genome Atlas. An important part of our argument are efficient and straightforward posterior simulation methods. We implement a variation of reversible jump Markov chain Monte Carlo simulation for inference under the DPP prior, using a density with respect to the unit rate Poisson process