Using Rb-TnSeq to Analyze Natural Variation in Saccharomyces cerevisiae

One of the main challenges in biology today is the characterization of millions of genes of unknown function being continuously identified in sequencing studies. Transposon mutagenesis is a technique that has been widely used for annotating gene function and has now been combined with next-generation sequencing (Tn-Seq) to assess mutant fitness on a genome wide basis. However, Tn-Seq approaches are often constrained by laborious library preparation protocols which limit the number of organisms or conditions that can be assessed. Random bar code transposon-site sequencing (RB-TnSeq), is a transposon sequencing technique that streamlines library preparation and increases the throughput of mutant fitness profiling by incorporating random DNA barcodes into Tn5 Transposons. Rb-TnSeq has been successfully used for high throughput mutant fitness assays in diverse bacterial species. However, this technique is yet to be applied to a eukaryotic model organism. The goal of this study is to develop tools that allow the construction of barcoded mutant libraries in saccharomyces cerevisiae and describes methods for producing barcoded mutant libraries using a plasmid based or transposome based approach. These library construction protocols can prove to be powerful tools for studying gene function in S. cerevisiae on a genome wide basis

Theory of the two-proton radioactivity in the continuum shell model

We develop the microscopic description of the two-nucleon radioactivity in the framework of the Shell Model Embedded in the Continuum. This approach is applied for the description of spontaneous two-proton radioactivity in $^{45}$Fe, $^{48}$Ni and $^{54}$Zn.Comment: 61 pages, 5 figure

On Probabilistic Parallel Programs with Process Creation and Synchronisation

We initiate the study of probabilistic parallel programs with dynamic process creation and synchronisation. To this end, we introduce probabilistic split-join systems (pSJSs), a model for parallel programs, generalising both probabilistic pushdown systems (a model for sequential probabilistic procedural programs which is equivalent to recursive Markov chains) and stochastic branching processes (a classical mathematical model with applications in various areas such as biology, physics, and language processing). Our pSJS model allows for a possibly recursive spawning of parallel processes; the spawned processes can synchronise and return values. We study the basic performance measures of pSJSs, especially the distribution and expectation of space, work and time. Our results extend and improve previously known results on the subsumed models. We also show how to do performance analysis in practice, and present two case studies illustrating the modelling power of pSJSs.Comment: This is a technical report accompanying a TACAS'11 pape

Automatic Enumeration of Generalized Menage Numbers

I describe an empirical-yet-rigorous, algorithm, based on Riordan's rook polynomials and the so-called C-finite ansatz, fully implemented in the accompanying Maple package (http://www.math.rutgers.edu/~zeilberg/tokhniot/MENAGES ), MENAGES, that reproduces in a few seconds, rigorously-proved enumeration theorems on permutations with restricted positions, previously proved by quite a few illustrious human mathematicians, and that can go far beyond any human attempts.Comment: 15 pages. An extended version of the last of three invited talks given by the author at the 71th Seminaire Lotharingien de Combinatoire, that took place in Bertinoro, Italy, Sept. 16-18, 201

Computational methods reveal novel functionalities of PIWI-interacting RNAs in human papillomavirus-induced head and neck squamous cell carcinoma.

Human papillomavirus (HPV) infection is the fastest growing cause of head and neck squamous cell carcinoma (HNSCC) today, but its role in malignant transformation remains unclear. This study aimed to conduct a comprehensive investigation of PIWI-interacting RNA (piRNA) alterations and functionalities in HPV-induced HNSCC. Using 77 RNA-sequencing datasets from TCGA, we examined differential expression of piRNAs between HPV16(+) HNSCC and HPV(-) Normal samples, identifying a panel of 30 HPV-dysregulated piRNAs. We then computationally investigated the potential mechanistic significances of these transcripts in HPV-induced HNSCC, identifying our panel of piRNAs to associate with the protein PIWIL4 as well as the RTL family of retrotransposon-like genes, possibly through direct binding interactions. We also recognized several HPV-dysregulated transcripts for their correlations with well-documented mutations and copy number variations in HNSCC as well as HNSCC clinical variables, demonstrating the potential ability of our piRNAs to play important roles in large-scale modulation of HNSCC in addition to their direct, smaller-scale interactions in this malignancy. The differential expression of key piRNAs, including NONHSAT077364, NONHSAT102574, and NONHSAT128479, was verified in vitro by evaluating endogenous expression in HPV(+) cancer vs. HPV(-) normal cell lines. Overall, our novel study provides a rigorous investigation of piRNA dysregulation in HPV-related HNSCC, and lends critical insight into the idea that these small regulatory transcripts may play crucial and previously unidentified roles in tumor pathogenesis and progression