Proteogenomic Analysis of Bacteria and Archaea: A 46 Organism Case Study

Experimental evidence is increasingly being used to reassess the quality and accuracy of genome annotation. Proteomics data used for this purpose, called proteogenomics, can alleviate many of the problematic areas of genome annotation, e.g. short protein validation and start site assignment. We performed a proteogenomic analysis of 46 genomes spanning eight bacterial and archaeal phyla across the tree of life. These diverse datasets facilitated the development of a robust approach for proteogenomics that is functional across genomes varying in %GC, gene content, proteomic sampling depth, phylogeny, and genome size. In addition to finding evidence for 682 novel proteins, 1336 new start sites, and numerous dubious genes, we discovered sites of post-translational maturation in the form of proteolytic cleavage of 1175 signal peptides. The number of novel proteins per genome is highly variable (median 7, mean 15, stdev 20). Moreover, comparison of novel genes with the current genes did not reveal any consistent abnormalities. Thus, we conclude that proteogenomics fulfills a yet to be understood deficiency in gene prediction. With the adoption of new sequencing technologies which have higher error rates than Sanger-based methods and the advances in proteomics, proteogenomics may become even more important in the future

A rapid biodiversity assessment of Papua New Guinea's Hindenburg Wall Region

[Extract] Aim: The Hindenburg Wall, along with the Muller Range and Nakanai Mountains, is a part of a proposed UNESCO World Heritage Site called The Sublime Karst of Papua New Guinea (Hamilton-Smith 2006). This survey document reports on a biodiversity assessment undertaken by the Wildlife Conservation Society Papua New Guinea (WCS), financed by the Papua New Guinea Sustainable Development Program Ltd (PNGSDP), and undertaken in partnership with the Papua New Guinea Department of Environment and Conservation (DEC). The aim of this project was to conduct a series of biological surveys in the region by a WCS-led team of international and nationaltaxonomic experts in order to investigate the biodiversity values in light of the area being a proposed UNESCO World Heritage Area

ANDES: Statistical tools for the ANalyses of DEep Sequencing

<p>Abstract</p> <p>Background</p> <p>The advancements in DNA sequencing technologies have allowed researchers to progress from the analyses of a single organism towards the deep sequencing of a sample of organisms. With sufficient sequencing depth, it is now possible to detect subtle variations between members of the same species, or between mixed species with shared biomarkers, such as the 16S rRNA gene. However, traditional sequencing analyses of samples from largely homogeneous populations are often still based on multiple sequence alignments (MSA), where each sequence is placed along a separate row and similarities between aligned bases can be followed down each column. While this visual format is intuitive for a small set of aligned sequences, the representation quickly becomes cumbersome as sequencing depths cover loci hundreds or thousands of reads deep.</p> <p>Findings</p> <p>We have developed ANDES, a software library and a suite of applications, written in Perl and R, for the statistical ANalyses of DEep Sequencing. The fundamental data structure underlying ANDES is the position profile, which contains the nucleotide distributions for each genomic position resultant from a multiple sequence alignment (MSA). Tools include the root mean square deviation (RMSD) plot, which allows for the visual comparison of multiple samples on a position-by-position basis, and the computation of base conversion frequencies (transition/transversion rates), variation (Shannon entropy), inter-sample clustering and visualization (dendrogram and multidimensional scaling (MDS) plot), threshold-driven consensus sequence generation and polymorphism detection, and the estimation of empirically determined sequencing quality values.</p> <p>Conclusions</p> <p>As new sequencing technologies evolve, deep sequencing will become increasingly cost-efficient and the inter and intra-sample comparisons of largely homogeneous sequences will become more common. We have provided a software package and demonstrated its application on various empirically-derived datasets. Investigators may download the software from Sourceforge at <url>https://sourceforge.net/projects/andestools</url>.</p

A rapid biodiversity assessment of Papua New Guinea's Hindenburg Wall Region

[Extract] Aim: The Hindenburg Wall, along with the Muller Range and Nakanai Mountains, is a part of a proposed UNESCO World Heritage Site called The Sublime Karst of Papua New Guinea (Hamilton-Smith 2006). This survey document reports on a biodiversity assessment undertaken by the Wildlife Conservation Society Papua New Guinea (WCS), financed by the Papua New Guinea Sustainable Development Program Ltd (PNGSDP), and undertaken in partnership with the Papua New Guinea Department of Environment and Conservation (DEC). The aim of this project was to conduct a series of biological surveys in the region by a WCS-led team of international and nationaltaxonomic experts in order to investigate the biodiversity values in light of the area being a proposed UNESCO World Heritage Area

Identification of proangiogenic genes and pathways by high-throughput functional genomics: TBK1 and the IRF3 pathway

A genome-wide phenotype screen was used to identify factors and pathways that induce proliferation of human umbilical vein endothelial cells (HUVEC). HUVEC proliferation is a recognized marker for factors that modulate vascularization. Screening “hits” included known proangiogenic factors, such as VEGF, FGF1, and FGF2 and additional factors for which a direct association with angiogenesis was not previously described. These include the kinase TBK1 as well as Toll-like receptor adaptor molecule and IFN regulatory factor 3. All three proteins belong to one signaling pathway that mediates induction of gene expression, including a mixture of secreted factors, which, in concert, mediate proliferative activity toward endothelial cells. TBK1 as the “trigger” of this pathway is induced under hypoxic conditions and expressed at significant levels in many solid tumors. This pattern of expression and the decreased expression of angiogenic factors in cultured cells upon RNA-interference-mediated ablation suggests that TBK1 is important for vascularization and subsequent tumor growth and a target for cancer therapy

Deep observations of Kepler's SNR with H.E.S.S.

Kepler’s supernova remnant (SNR) which is produced by the most recent naked-eye supernova in our Galaxy is one of the best studied SNRs, but its gamma-ray detection has eluded us so far. Observations with modern imaging atmospheric Cherenkov telescopes (IACT) have enlarged the knowledge about nearby SNRs with ages younger than 500 years by establishing Cassiopeia A and Tycho’s SNRs as very high energy (VHE) gamma-ray sources and setting a lower limit on the distance to Kepler’s SNR. This SNR is significantly more distant than the other two and expected to be one of the faintest gamma-ray sources within reach of the IACT arrays of this generation. We report strong evidence for a VHE signal from Kepler’s SNR based on deep observations of the High Energy Stereoscopic System (H.E.S.S.) with an exposure of 152 hours, including 122 hours accumulated in 2017-2020. We further discuss implications of this result for cosmic-ray acceleration in young SNRs

Observation of burst activity from SGR1935+2154 associated to first galactic FRB with H.E.S.S.

Fast radio bursts (FRB) are enigmatic powerful single radio pulses with durations of several milliseconds and high brightness temperatures suggesting coherent emission mechanism. For the time being a number of extragalactic FRBs have been detected in the high-frequency radio band including repeating ones. The most plausible explanation for these phenomena is magnetar hyperflares. The first observational evidence of this scenario was obtained in April 2020 when an FRB was detected from the direction of the Galactic magnetar and soft gamma repeater SGR1935+2154. The FRB was preceded with a number of soft gamma-ray bursts observed by Swift-BAT satellite, which triggered the follow-up program of the H.E.S.S. imaging atmospheric Cherenkov telescopes (IACTs). H.E.S.S. has observed SGR1935+2154 over a 2 hour window few hours prior to the FRB detection by STARE2 and CHIME. The observations overlapped with other X-ray bursts from the magnetar detected by INTEGRAL and Swift-BAT, thus providing first observations of a magnetar in a flaring state in the very-high energy domain. We present the analysis of these observations, discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma repeaters and anomalous X-ray pulsars

Observation of burst activity from SGR1935+2154 associated to first galactic FRB with H.E.S.S.

Fast radio bursts (FRB) are enigmatic powerful single radio pulses with durations of several milliseconds and high brightness temperatures suggesting coherent emission mechanism. For the time being a number of extragalactic FRBs have been detected in the high-frequency radio band including repeating ones. The most plausible explanation for these phenomena is magnetar hyperflares. The first observational evidence of this scenario was obtained in April 2020 when an FRB was detected from the direction of the Galactic magnetar and soft gamma repeater SGR1935+2154. The FRB was preceded with a number of soft gamma-ray bursts observed by Swift-BAT satellite, which triggered the follow-up program of the H.E.S.S. imaging atmospheric Cherenkov telescopes (IACTs). H.E.S.S. has observed SGR1935+2154 over a 2 hour window few hours prior to the FRB detection by STARE2 and CHIME. The observations overlapped with other X-ray bursts from the magnetar detected by INTEGRAL and Swift-BAT, thus providing first observations of a magnetar in a flaring state in the very-high energy domain. We present the analysis of these observations, discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma repeaters and anomalous X-ray pulsars