Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis

Sequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC4E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms

Comparative genomics of tadpole shrimps (Crustacea, Branchiopoda, Notostraca): Dynamic genome evolution against the backdrop of morphological stasis

This analysis presents five genome assemblies of four Notostraca taxa. Notostraca origin dates to the Permian/Upper Devonian and the extant forms show a striking morphological similarity to fossil taxa. The comparison of sequenced genomes with other Branchiopoda genomes shows that, despite the morphological stasis, Notostraca share a dynamic genome evolution with high turnover for gene families' expansion/contraction and a transposable elements content comparable to other branchiopods. While Notostraca substitutions rate appears similar or lower in comparison to other branchiopods, a subset of genes shows a faster evolutionary pace, highlighting the difficulty of generalizing about genomic stasis versus dynamism. Moreover, we found that the variation of Triops cancriformis transposable elements content appeared linked to reproductive strategies, in line with theoretical expectations. Overall, besides providing new genomic resources for the study of these organisms, which appear relevant for their ecology and evolution, we also confirmed the decoupling of morphological and molecular evolution

A primary breast cancer with distinct foci of estrogen receptor-alpha positive and negative cells derived from the same clonal origin as revealed by whole exome sequencing

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background/purpose: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. Experimental design/methods: Here, we present a case report of a patient’s primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative. Each component was subjected to whole exome sequencing and compared for gene identity to determine clonal origin. Results: Using prior bioinformatic tools, we demonstrated that both the ER positive and negative components shared many variants, including passenger and driver alterations. Copy number variations also supported the two components were derived from a single common clone. Conclusions: These analyses strongly suggest that the two ER components of this patient’s breast cancer were derived from the same clonal origin. Our results have implications for the evolution of breast cancers with mixed histologies, and how they might be best managed for optimal therapy

A quasi classical approach to electron impact ionization

A quasi classical approximation to quantum mechanical scattering in the Moeller formalism is developed. While keeping the numerical advantage of a standard Classical--Trajectory--Monte--Carlo calculation, our approach is no longer restricted to use stationary initial distributions. This allows one to improve the results by using better suited initial phase space distributions than the microcanonical one and to gain insight into the collision mechanism by studying the influence of different initial distributions on the cross section. A comprehensive account of results for single, double and triple differential cross sections for atomic hydrogen will be given, in comparison with experiment and other theories.Comment: 21 pages, 10 figures, submitted to J Phys

Team level identification predicts perceived and actual team performance: longitudinal multilevel analyses with sports teams

Social identification and team performance literatures typically focus on the relationship between individual differences in identification and individual-level performance. By using a longitudinal multilevel approach, involving 369 members of 45 sports teams across England and Italy, we compared how team-level and individual-level variance in social identification together predicted team and individual performance outcomes. As hypothesised, team-level variance in identification significantly predicted subsequent levels of both perceived and actual team performance in cross-lagged analyses. Conversely, individual-level variance in identification did not significantly predict subsequent levels of perceived individual performance. These findings support recent calls for social identity to be considered a multilevel construct and highlight the influence of group-level social identification on group-level processes and outcomes, over and above its individual-level effects

Establishing the baseline level of repetitive element expression in the human cortex

Background: Although nearly half of the human genome is comprised of repetitive sequences, the expression profile of these elements remains largely uncharacterized. Recently developed high throughput sequencing technologies provide us with a powerful new set of tools to study repeat elements. Hence, we performed whole transcriptome sequencing to investigate the expression of repetitive elements in human frontal cortex using postmortem tissue obtained from the Stanley Medical Research Institute. Results: We found a significant amount of reads from the human frontal cortex originate from repeat elements. We also noticed that Alu elements were expressed at levels higher than expected by random or background transcription. In contrast, L1 elements were expressed at lower than expected amounts. Conclusions: Repetitive elements are expressed abundantly in the human brain. This expression pattern appears to be element specific and can not be explained by random or background transcription. These results demonstrate that our knowledge about repetitive elements is far from complete. Further characterization is required to determine the mechanism, the control, and the effects of repeat element expression

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

BACKGROUND: Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM) approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix), secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. RESULTS: Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. CONCLUSION: Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset

The PKA-CREB system encoded by the honeybee genome

The cAMP-dependent kinase (PKA) plays a crucial part in long-term memory formation in the honeybee (Apis mellifera). One of the putative substrates of the PKA activity is the cAMP response element binding protein (CREB), a transcription factor in the bZIP protein family. We searched the honeybee genome to characterize genes from the CREB/CREM and the PKA families. We identified two genes that encode regulatory subunits and three genes encode catalytic subunits of PKA. Eight genes code for bZIP proteins, but only one gene was found that encodes a member of the CREB/CREM family. The phylogenetic relationship of these genes was analysed with their Drosophila and human counterparts