Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network.

Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function.

Antagonism between bacteriostatic and bactericidal antibiotics is prevalent.

Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug.

Bacterial evolution of antibiotic hypersensitivity.

The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics.

Semi-automated construction of decision rules to predict morbidities from clinical texts.

OBJECTIVE In this study the authors describe the system submitted by the team of University of Szeged to the second i2b2 Challenge in Natural Language Processing for Clinical Data. The challenge focused on the development of automatic systems that analyzed clinical discharge summary texts and addressed the following question: "Who's obese and what co-morbidities do they (definitely/most likely) have?". Target diseases included obesity and its 15 most frequent comorbidities exhibited by patients, while the target labels corresponded to expert judgments based on textual evidence and intuition (separately).

Protein classification based on propagation of unrooted binary trees.

We present two efficient network propagation algorithms that operate on a binary tree, i.e., a sparse-edged substitute of an entire similarity network.

State-of-the-art anonymization of medical records using an iterative machine learning framework.

Objective: The anonymization of medical records is of great importance in the human life sciences because a de-identified text can be made publicly available for non-hospital researchers as well, to facilitate research on human diseases. Here the authors have developed a de-identification model that can successfully remove personal health information (PHI) from discharge records to make them conform to the guidelines of the Health Information Portability and Accountability Act.

Design: We introduce here a novel, machine learning-based iterative Named Entity Recognition approach intended for use on semi-structured documents like discharge records.

Balanced ROC analysis (BAROC) protocol for the evaluation of protein similarities.

Identification of problematic protein classes (domain types, protein families) that are difficult to predict from sequence is a key issue in genome annotation. ROC (Receiver Operating Characteristic) analysis is routinely used for the evaluation of protein similarities, however its results - the area under curve (AUC) values - are differentially biased for the various protein classes that are highly different in size. We show the bias can be compensated for by adjusting the length of the top list in a class-dependent fashion, so that the number of negatives within the top list will be equal to (or proportional with) the size of the positive class.