N. Davidson

Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes

The condensin complex is essential for correct packaging and segregation of chromosomes during mitosis and meiosis in all eukaryotes. To date, the genome-wide location and the nature of condensin-binding sites have remained elusive in vertebrates. Here we report the genome-wide map of condensin I in chicken DT40 cells. Unexpectedly, we find that condensin I binds predominantly to promoter sequences in mitotic cells. We also find a striking enrichment at both centromeres and telomeres, highlighting the importance of the complex in chromosome segregation. Taken together, the results show that condensin I is largely absent from heterochromatic regions. This map of the condensin I binding sites on the chicken genome reveals that patterns of condensin distribution on chromosomes are conserved from prokaryotes, through yeasts to vertebrates. Thus in three kingdoms of life, condensin is enriched on promoters of actively transcribed genes and at loci important for chromosome segregation.

MC-TESTER v. 1.23: a universal tool for comparisons of Monte Carlo predictions for particle decays in high energy physics †

Abstract Theoretical predictions in high energy physics are routinely provided in the form of Monte Carlo generators. Comparisons of predictions from different programs and/or different initialization set-ups are often necessary. MC-TESTER can be used for such tests of decays of intermediate states (particles or resonances) in a semi-automated way. Since 2002 new functionalities were introduced into the package. In particular, it now works with the HepMC event record, the standard for C++ programs. The complete set-up for benchmarking the interfaces, such as interface between τ-lepton production and decay, including QED bremsstrahlung effects is shown. The example is chosen to illustrate the new options introduced into the program. From the technical perspective, our paper documents software updates and supplements previous documentation. As in the past, our test consists of two steps. Distinct Monte Carlo programs are run separately; events with decays of a chosen particle are searched, and information is stored by MC-TESTER . Then, at the analysis step, information from a pair of runs may be compared and represented in the form of tables and plots. Updates introduced in the program up to version 1.24.4 are also documented. In particular, new configuration scripts or script to combine results from multitude of runs into single information file to be used in analysis step are explained. Program summary Program title: MC-TESTER, version 1.23 and version 1.24.4 Catalog identifier: ADSM_v2_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/ADSM_v2_0.html Program obtainable from: CPC Program Library, Queens University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 250 548 No. of bytes in distributed program, including test data, etc.: 4 290 610 Distribution format: tar.gz Programming language: C++, FORTRAN77 Tested and compiled with: gcc 3.4.6, 4.2.4 and 4.3.2 with g77/gfortran Computer: Tested on various platforms Operating system: Tested on operating systems: Linux SLC 4.6 and SLC 5, Fedora 8, Ubuntu 8.2 etc. Classification: 11.9 External routines: HepMC ( https://savannah.cern.ch/projects/hepmc/ ), PYTHIA8 ( http://home.thep.lu.se/~torbjorn/Pythia.html ), LaTeX ( http://www.latex-project.org/ ) Catalog identifier of previous version: ADSM_v1_0 Journal reference of previous version: Comput. Phys. Comm. 157 (2004) 39 Does the new version supersede the previous version?: Yes Nature of problem: The decays of individual particles are well defined modules of a typical Monte Carlo program chain in high energy physics. A fast, semi-automatic way of comparing results from different programs is often desirable for the development of new programs, in order to check correctness of the installations or for discussion of uncertainties. Solution method: A typical HEP Monte Carlo program stores the generated events in event records such as HepMC, HEPEVT or PYJETS. MC-TESTER scans, event by event, the contents of the record and searches for the decays of the particle under study. The list of the found decay modes is successively incremented and histograms of all invariant masses which can be calculated from the momenta of the particle decay products are defined and filled. The outputs from the two runs of distinct programs can be later compared. A booklet of comparisons is created: for every decay channel, all histograms present in the two outputs are plotted and parameter quantifying shape difference is calculated. Its maximum over every decay channel is printed in the summary table. Reasons for new version: Interface for HepMC Event Record is introduced. Setup for benchmarking the interfaces, such as τ-lepton production and decay, including QED bremsstrahlung effects is introduced as well. This required significant changes in the algorithm. As a consequence, a new version of the code was introduced. Summary of revisions: • HepMC interface introduced • installation and configuration scripts added • visualization options added • introduced options useful for use of the program on distributed systems, such as the grid • comments regarding source code added Restrictions: Only the first 200 decay channels that were found will initialize histograms and if the multiplicity of decay products in a given channel was larger than 7, histograms will not be created for that channel. Additional comments: New features: HepMC interface, use of lists in definition of histograms and decay channels, filters for decay products or secondary decays to be omitted, bug fixing, extended flexibility in representation of program output, installation configuration scripts, merging multiple output files from separate generations. Running time: Varies substantially with the analyzed decay particle, but generally speed estimation of the old version remains valid. On a PC/Linux with 2.0 GHz processors MC-TESTER increases the run time of the τ-lepton Monte Carlo program TAUOLA by 4.0 seconds for every 100 000 analyzed events (generation itself takes 26 seconds). The analysis step takes 13 seconds; LATEX processing takes additionally 10 seconds. Generation step runs may be executed simultaneously on multiprocessor machines.

SuperTranscripts: a data driven reference for analysis and visualisation of transcriptomes

Numerous methods have been developed to analyse RNA sequencing (RNA-seq) data, but most rely on the availability of a reference genome, making them unsuitable for non-model organisms. Here we present superTranscripts, a substitute for a reference genome, where each gene with multiple transcripts is represented by a single sequence. The Lace software is provided to construct superTranscripts from any set of transcripts, including de novo assemblies. We demonstrate how superTranscripts enable visualisation, variant detection and differential isoform detection in non-model organisms. We further use Lace to combine reference and assembled transcriptomes for chicken and recover hundreds of gaps in the reference genome.

Necklace: combining reference and assembled transcriptomes for more comprehensive RNA-Seq analysis

Abstract Background RNA sequencing (RNA-seq) analyses can benefit from performing a genome-guided and de novo assembly, in particular for species where the reference genome or the annotation is incomplete. However, tools for integrating an assembled transcriptome with reference annotation are lacking. Findings Necklace is a software pipeline that runs genome-guided and de novo assembly and combines the resulting transcriptomes with reference genome annotations. Necklace constructs a compact but comprehensive superTranscriptome out of the assembled and reference data. Reads are subsequently aligned and counted in preparation for differential expression testing. Conclusions Necklace allows a comprehensive transcriptome to be built from a combination of assembled and annotated transcripts, which results in a more comprehensive transcriptome for the majority of organisms. In addition RNA-seq data are mapped back to this newly created superTranscript reference to enable differential expression testing with standard methods.

Clinker: visualizing fusion genes detected in RNA-seq data

ABSTRACT Background Genomic profiling efforts have revealed a rich diversity of oncogenic fusion genes. While there are many methods for identifying fusion genes from RNA-sequencing (RNA-seq) data, visualizing these transcripts and their supporting reads remains challenging. Findings Clinker is a bioinformatics tool written in Python, R, and Bpipe that leverages the superTranscript method to visualize fusion genes. We demonstrate the use of Clinker to obtain interpretable visualizations of the RNA-seq data that lead to fusion calls. In addition, we use Clinker to explore multiple fusion transcripts with novel breakpoints within the P2RY8-CRLF2 fusion gene in B-cell acute lymphoblastic leukemia. Conclusions Clinker is freely available software that allows visualization of fusion genes and the RNA-seq data used in their discovery.

Necklace: combining reference and assembled transcriptomes for RNA-Seq analysis

Background RNA-Seq analyses can benefit from performing a genome-guided and de novo assembly, in particular for species where the reference genome or the annotation is incomplete. However, tools for integrating assembled transcriptome with reference annotation are lacking. Findings Necklace is a software pipeline that runs genome-guided and de novo assembly and combines the resulting transcriptomes with reference genome annotations. Necklace constructs a compact but comprehensive superTranscriptome out of the assembled and reference data. Reads are subsequently aligned and counted in preparation for differential expression testing. Conclusions Necklace allows a comprehensive transcriptome to be built from a combination of assembled and annotated transcripts which results in a more comprehensive transcriptome for the majority of organisms. In addition RNA-seq data is mapped back to this newly created superTranscript reference to enable differential expression testing with standard methods. Necklace is available from https://github.com/Oshlack/necklace/wiki under GPL 3.0.

SuperTranscript: a reference for analysis and visualization of the transcriptome

Numerous methods have been developed to analyse RNA sequencing data, but most rely on the availability of a reference genome, making them unsuitable for non-model organisms. De novo transcriptome assembly can build a reference transcriptome from the non-model sequencing data, but falls short of allowing most tools to be applied. Here we present superTranscripts, a simple but powerful solution to bridge that gap. SuperTranscripts are a substitute for a reference genome, consisting of all the unique exonic sequence, in transcriptional order, such that each gene is represented by a single sequence. We demonstrate how superTranscripts allow visualization, variant detection and differential isoform detection in non-model organisms, using widely applied methods that are designed to work with reference genomes. SuperTranscripts can also be applied to model organisms to enhance visualization and discover novel expressed sequence. We describe Lace, software to construct superTranscripts from any set of transcripts including de novo assembled transcriptomes. In addition we used Lace to combine reference and assembled transcriptomes for chicken and recovered the sequence of hundreds of gaps in the reference genome.