The input to an algorithm that learns a binary classifier normally consists of two sets of examples, where one set consists of positive examples of the concept to be learned, and the other set consists of negative examples. However, it is often the case that the available training data are an incomplete set of positive examples, and a set of unlabeled examples, some of which are positive and some of which are negative. The problem solved in this paper is how to learn a standard binary classifier given a nontraditional training set of this nature.Under the assumption that the labeled examples are selected randomly from the positive examples, we show that a classifier trained on positive and unlabeled examples predicts probabilities that differ by only a constant factor from the true conditional probabilities of being positive. We show how to use this result in two different ways to learn a classifier from a nontraditional training set. We then apply these two new methods to solve a real-world problem: identifying protein records that should be included in an incomplete specialized molecular biology database. Our experiments in this domain show that models trained using the new methods perform better than the current state-of-the-art biased SVM method for learning from positive and unlabeled examples.

The Transporter Classification Database (TCDB; http://www.tcdb.org) is a freely accessible reference database for transport protein research, which provides structural, functional, mechanistic, evolutionary and disease/medical information about transporters from organisms of all types. TCDB is the only transport protein classification database adopted by the International Union of Biochemistry and Molecular Biology (IUBMB). It consists of more than 10 000 non-redundant transport systems with more than 11 000 reference citations, classified into over 1000 transporter families. Transporters in TCDB can be single or multi-component systems, categorized in a functional/phylogenetic hierarchical system of classes, subclasses, families, subfamilies and transport systems. TCDB also includes updated software designed to analyze the distinctive features of transport proteins, extending its usefulness. Here we present a comprehensive update of the database contents and features and summarize recent discoveries recorded in TCDB.

Despite strides in characterizing human history from genetic polymorphism data, progress in identifying genetic signatures of recent demography has been limited. Here we identify very recent fine-scale population structure in North America from a network of over 500 million genetic (identity-by-descent, IBD) connections among 770,000 genotyped individuals of US origin. We detect densely connected clusters within the network and annotate these clusters using a database of over 20 million genealogical records. Recent population patterns captured by IBD clustering include immigrants such as Scandinavians and French Canadians; groups with continental admixture such as Puerto Ricans; settlers such as the Amish and Appalachians who experienced geographic or cultural isolation; and broad historical trends, including reduced north-south gene flow. Our results yield a detailed historical portrait of North America after European settlement and support substantial genetic heterogeneity in the United States beyond that uncovered by previous studies.

BackgroundDetermining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them.ResultsA total of 11 teams participated in at least one of the two PPI tasks (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as participants or in preparing data sets/evaluating these tasks. Per task, each team was allowed to submit five runs offline and another five online via the BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of 89% and the best AUC iP/R was 68%. Most ACT teams explored machine learning methods, some of them also used lexical resources like MeSH terms, PSI-MI concepts or particular lists of verbs and nouns, some integrated NER approaches. For the IMT, a total of 42 runs were evaluated by comparing systems against manually generated annotations done by curators from the BioGRID and MINT databases. The highest AUC iP/R achieved by any run was 53%, the best MCC score 0.55. In case of competitive systems with an acceptable recall (above 35%) the macro-averaged precision ranged between 50% and 80%, with a maximum F-Score of 55%.ConclusionsThe results of the ACT task of BioCreative III indicate that classification of large unbalanced article collections reflecting the real class imbalance is still challenging. Nevertheless, text-mining tools that report ranked lists of relevant articles for manual selection can potentially reduce the time needed to identify half of the relevant articles to less than 1/4 of the time when compared to unranked results. Detecting associations between full text articles and interaction detection method PSI-MI terms (IMT) is more difficult than might be anticipated. This is due to the variability of method term mentions, errors resulting from pre-processing of articles provided as PDF files, and the heteroge...

Here, Ruby et al. analyze an unprecedented amount of public family tree data from Ancestry and determine that the heritability of human longevity was well below 10%, lower than the widely-held belief that lifespan...