Population gene introgression and high genome plasticity for the zoonotic pathogen Streptococcus agalactiae

The influence that bacterial adaptation (or niche partitioning) within species has on gene spillover and transmission among bacteria populations occupying different niches is not well understood. Streptococcus agalactiae is an important bacterial pathogen that has a taxonomically diverse host range making it an excellent model system to study these processes. Here we analyze a global set of 901 genome sequences from nine diverse host species to advance our understanding of these processes. Bayesian clustering analysis delineated twelve major populations that closely aligned with niches. Comparative genomics revealed extensive gene gain/loss among populations and a large pan-genome of 9,527 genes, which remained open and was strongly partitioned among niches. As a result, the biochemical characteristics of eleven populations were highly distinctive (significantly enriched). Positive selection was detected and biochemical characteristics of the dispensable genes under selection were enriched in ten populations. Despite the strong gene partitioning, phylogenomics detected gene spillover. In particular, tetracycline resistance (which likely evolved in the human-associated population) from humans to bovine, canines, seals, and fish, demonstrating how a gene selected in one host can ultimately be transmitted into another, and biased transmission from humans to bovines was confirmed with a Bayesian migration analysis. Our findings show high bacterial genome plasticity acting in balance with selection pressure from distinct functional requirements of niches that is associated with an extensive and highly partitioned dispensable genome, likely facilitating continued and expansive adaptation

Knowledge Base Population using Semantic Label Propagation

A crucial aspect of a knowledge base population system that extracts new facts from text corpora, is the generation of training data for its relation extractors. In this paper, we present a method that maximizes the effectiveness of newly trained relation extractors at a minimal annotation cost. Manual labeling can be significantly reduced by Distant Supervision, which is a method to construct training data automatically by aligning a large text corpus with an existing knowledge base of known facts. For example, all sentences mentioning both 'Barack Obama' and 'US' may serve as positive training instances for the relation born_in(subject,object). However, distant supervision typically results in a highly noisy training set: many training sentences do not really express the intended relation. We propose to combine distant supervision with minimal manual supervision in a technique called feature labeling, to eliminate noise from the large and noisy initial training set, resulting in a significant increase of precision. We further improve on this approach by introducing the Semantic Label Propagation method, which uses the similarity between low-dimensional representations of candidate training instances, to extend the training set in order to increase recall while maintaining high precision. Our proposed strategy for generating training data is studied and evaluated on an established test collection designed for knowledge base population tasks. The experimental results show that the Semantic Label Propagation strategy leads to substantial performance gains when compared to existing approaches, while requiring an almost negligible manual annotation effort.Comment: Submitted to Knowledge Based Systems, special issue on Knowledge Bases for Natural Language Processin

A Data-Driven Behavior Modeling and Analysis Framework for Diabetic Patients on Insulin Pumps

About 30%-40% of Type 1 Diabetes (T1D) patients in the United States use insulin pumps. Current insulin infusion systems require users to manually input meal carb count and approve or modify the system-suggested meal insulin dose. Users can give correction insulin boluses at any time. Since meal carbohydrates and insulin are the two main driving forces of the glucose physiology, the user-specific eating and pump-using behavior has a great impact on the quality of glycemic control. In this paper, we propose an “Eat, Trust, and Correct” (ETC) framework to model the T1D insulin pump users’ behavior. We use machine learning techniques to analyze the user behavior from a clinical dataset that we collected on 55 T1D patients who use insulin pumps. We demonstrate the usefulness of the ETC behavior modeling framework by performing in silico experiments. To this end, we integrate the user behavior model with an individually parameterized glucose physiological model, and perform probabilistic model checking on the user-in-the-loop system. The experimental results show that switching behavior types can significantly improve a patient’s glycemic control outcomes. These analysis results can boost the effectiveness of T1D patient education and peer support

Pattern discovery in structural databases with applications to bioinformatics

Frequent structure mining (FSM) aims to discover and extract patterns frequently occurring in structural data such as trees and graphs. FSM finds many applications in bioinformatics, XML processing, Web log analysis, and so on. In this thesis, two new FSM techniques are proposed for finding patterns in unordered labeled trees. Such trees can be used to model evolutionary histories of different species, among others. The first FSM technique finds cousin pairs in the trees. A cousin pair is a pair of nodes sharing the same parent, the same grandparent, or the same great-grandparent, etc. Given a tree T, our algorithm finds all interesting cousin pairs of T in O(|T|2) time where |T| is the number of nodes in T. Experimental results on synthetic data and phylogenies show the scalability and effectiveness of the proposed technique. This technique has been applied to locating co-occurring patterns in multiple evolutionary trees, evaluating the consensus of equally parsimonious trees, and finding kernel trees of groups of phylogenies. The technique is also extended to undirected acyclic graphs (or free trees). The second FSM technique extends traditional MAST (maximum agreement subtree) algorithms by employing the Apriori data mining technique to find frequent agreement subtrees in multiple phylogenies. The correctness and completeness of the new mining algorithm are presented. The method is also extended to unrooted phylogenetic trees. Both FSM techniques studied in the thesis have been implemented into a toolkit, which is fully operational and accessible on the World Wide Web