Novel bioinformatics quality control metric for next-generation sequencing experiments in the clinical context

As the use of next-generation sequencing (NGS) for the Mendelian diseases diagnosis is expanding, the performance of this method has to be improved in order to achieve higher quality. Typically, performance measures are considered to be designed in the context of each application and, therefore, account for a spectrum of clinically relevant variants. We present EphaGen, a new computational methodology for bioinformatics quality control (QC). Given a single NGS dataset in BAM format and a pre-compiled VCF-file of targeted clinically relevant variants it associates this dataset with a single arbiter parameter. Intrinsically, EphaGen estimates the probability to miss any variant from the defined spectrum within a particular NGS dataset. Such performance measure virtually resembles the diagnostic sensitivity of given NGS dataset. Here we present case studies of the use of EphaGen in context of BRCA1/2 and CFTR sequencing in a series of 14 runs across 43 blood samples and 504 publically available NGS datasets. EphaGen is superior to conventional bioinformatics metrics such as coverage depth and coverage uniformity. We recommend using this software as a QC step in NGS studies in the clinical context. Availability: https://github.com/m4merg/EphaGen or https://hub.docker.com/r/m4merg/ephagen.

Varieties of abstract concepts and their multiple dimensions

abstractThe issue of how abstract concepts are represented is widely debated. However, evidence is controversial, also because different criteria were used to select abstract concepts – for example, imageability and abstractness were equated. In addition, for many years abstract concepts have been considered as a unitary whole. Our work aims to address these two limitations. We asked participants to evaluate 425 abstract concepts on 15 dimensions: abstractness, concreteness, imageability, context availability, Body-Object-Interaction, Modality of Acquisition, Age of Acquisition, Perceptual modality strength, Metacognition, Social metacognition, Interoception, Emotionality, Social valence, Hand and Mouth activation. Results showed that conceiving concepts only in terms of concreteness/abstractness is too simplified. More abstract concepts are typically acquired later and through the linguistic modality and are characterized by high scores in social metacognition (feeling that others can help us in understanding word meaning), while concrete concepts obtain high scores in Body-Object-Interaction, imageability, and context availability. A cluster analysis indicated four kinds of abstract concepts: philosophical-spiritual (e.g., value), self-sociality (e.g., politeness), emotive/inner states (e.g., anger), and physical, spatio-temporal, and quantitative concepts (e.g., reflex). Overall, results support multiple representation views indicating that sensorimotor, inner, linguistic, and social experience have different weights in characterizing different kinds of abstract concepts.

Mapping concrete and abstract meanings to new words using verbal contexts

In three experiments, we examine the effects of semantic context and word concreteness on the mapping of existing meanings to new words. We developed a new-word-learning paradigm in which participants were required to discover the meaning of a new-word form from a specific verbal context. The stimulus materials were manipulated according to word concreteness, context availability and semantic congruency across contexts. Overall, participants successfully learned the meaning of the new word whether it was a concrete or an abstract word. Concrete word meanings were discovered and learned faster than abstract word meanings even when matched on context availability. The present results are discussed considering the various hypotheses that have been used to try to explain the ‘concreteness effect’. We conclude that the present investigation provides new evidence that the concreteness effect observed in learning is due to the different organization of abstract and concrete conceptual information in semantic memory.