Bigram - PGK: phosphoglycerylation prediction using the technique of bigram probabilities of position specific scoring matrix

Background: The biological process known as post-translational modification (PTM) is a condition whereby proteomes are modified that affects normal cell biology, and hence the pathogenesis. A number of PTMs have been discovered in the recent years and lysine phosphoglycerylation is one of the fairly recent developments. Even with a large number of proteins being sequenced in the post-genomic era, the identification of phosphoglycerylation remains a big challenge due to factors such as cost, time consumption and inefficiency involved in the experimental efforts. To overcome this issue, computational techniques have emerged to accurately identify phosphoglycerylated lysine residues. However, the computational techniques proposed so far hold limitations to correctly predict this covalent modification. Results: We propose a new predictor in this paper called Bigram-PGK which uses evolutionary information of amino acids to try and predict phosphoglycerylated sites. The benchmark dataset which contains experimentally labelled sites is employed for this purpose and profile bigram occurrences is calculated from position specific scoring matrices of amino acids in the protein sequences. The statistical measures of this work, such as sensitivity, specificity, precision, accuracy, Mathews correlation coefficient and area under ROC curve have been reported to be 0.9642, 0.8973, 0.8253, 0.9193, 0.8330, 0.9306, respectively. Conclusions: The proposed predictor, based on the feature of evolutionary information and support vector machine classifier, has shown great potential to effectively predict phosphoglycerylated and non-phosphoglycerylated lysine residues when compared against the existing predictors. The data and software of this work can be acquired from https://github.com/abelavit/Bigram-PGK

Mutational landscape of RNA-binding proteins in human cancers

RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations. Functional analysis of these RBPs revealed the enrichment of pathways associated with apoptosis, splicing and translation. Using the OncodriveFM framework, we also identified more than 200 candidate driver RBPs that were found to accumulate functionally impactful mutations in at least one cancer. Expression levels of 15% of these driver RBPs exhibited significant difference, when transcriptome groups with and without deleterious mutations were compared. Functional interaction network of the driver RBPs revealed the enrichment of spliceosomal machinery, suggesting a plausible mechanism for tumorogenesis while network analysis of the protein interactions between RBPs unambiguously revealed the higher degree, betweenness and closeness centrality for driver RBPs compared to non-drivers. Analysis to reveal cancer-specific Ribonucleoprotein (RNP) mutational hotspots showed extensive rewiring even among common drivers between cancer types. Knockdown experiments on pan-cancer drivers such as SF3B1 and PRPF8 in breast cancer cell lines, revealed cancer subtype specific functions like selective stem cell features, indicating a plausible means for RBPs to mediate cancer-specific phenotypes. Hence, this study would form a foundation to uncover the contribution of the mutational spectrum of RBPs in dysregulating the post-transcriptional regulatory networks in different cancer types

Data-driven honeybee antennal lobe model suggests how stimulus-onset asynchrony can aid odour segregation

Insects have a remarkable ability to identify and track odour sources in multi-odour backgrounds. Recent behavioural experiments show that this ability relies on detecting millisecond stimulus asynchronies between odourants that originate from different sources. Honeybees, Apis mellifera , are able to distinguish mixtures where both odourants arrive at the same time (synchronous mixtures) from those where odourant onsets are staggered (asynchronous mixtures) down to an onset delay of only 6 ms. In this paper we explore this surprising ability in a model of the insects' primary olfactory brain area, the antennal lobe. We hypothesize that a winner-take-all inhibitory network of local neurons in the antennal lobe has a symmetry-breaking effect, such that the response pattern in projection neurons to an asynchronous mixture is different from the response pattern to the corresponding synchronous mixture for an extended period of time beyond the initial odourant onset where the two mixture conditions actually differ. The prolonged difference between response patterns to synchronous and asynchronous mixtures could facilitate odour segregation in downstream circuits of the olfactory pathway. We present a detailed data-driven model of the bee antennal lobe that reproduces a large data set of experimentally observed physiological odour responses, successfully implements the hypothesised symmetry-breaking mechanism and so demonstrates that this mechanism is consistent with our current knowledge of the olfactory circuits in the bee brain

Is GRB 050904 at z=6.3 absorbed by dust?

Claim of dust extinction for this GRB has been debated in the past. We suggest that the discrepant results occur primarily because most of previous studies have not simultaneously investigated the X-ray to near-IR spectral energy distribution of this GRB. The difficulty with this burst is that the X-ray afterglow is dominated by strong flares at early times and is poorly monitored at late times. In addition, the Z band photometry, which is the most sensitive to dust extinction, has been found to be affected by strong systematics. In this paper we carefully re-analyze the Swift/XRT afterglow observations of this GRB, using extensive past studies of X-ray flare properties when computing the X-ray afterglow flux level and exploiting the recent reanalysis of the optical (UV rest frame) data of the same GRB. We extract the X-ray to optical/near-IR afterglow SED for the three epochs where the best spectral coverage is available: 0.47, 1.25, and 3.4 days after the trigger. A spectral power-law model has been fitted to the extracted SEDs. We discuss that no spectral breaks or chromatic temporal breaks are expected in the epochs of interest. To fit any UV rest-frame dust absorption, we tested the Small Magellanic Cloud (SMC) extinction curve, the mean extinction curve (MEC) found for a sample of QSO at $z>4$ and its corresponding attenuation curve, as well as a starburst attenuation curve, and the extinction curve consistent with a supernova dust origin (SN-type). The SMC extinction curve and the SN-type one provide good fit to the data at all epochs, with an average amount of dust absorption at $\lambda_{rest} = 3000 \AA$ of $A_{3000} = 0.25\pm 0.07$ mag. These results indicate that the primeval galaxy at $z = 6.3$ hosting this GRB has already enriched its ISM with dust.Comment: 8 pages, 3 figures, accepted for publication in Astronomy and Astrophysics; figure 1 has been degraded, full resolution version at http://dl.dropbox.com/u/1670579/fig01.p

Comparing oncologic outcomes in patients undergoing surgery for oncocytic neoplasms, conventional oncocytoma, and chromophobe renal cell carcinoma

Introduction Oncocytic neoplasms are renal tumors similar to oncocytoma, but their morphologic variations preclude definitive diagnosis. This somewhat confusing diagnosis can create treatment and surveillance challenges for the treating urologist. We hypothesize that these subtle morphologic variations do not drastically affect the malignant potential of these tumors, and we sought to demonstrate this by comparing clinical outcomes of oncocytic neoplasms to those of classic oncocytoma and chromophobe. Methods We gathered demographic and outcomes data for patients with variant oncocytic tumors. Oncologic surveillance was conducted per institutional protocol in accordance with NCCN guidelines. Descriptive statistics were used to compare incidence of metastasis and death against those for patients with oncocytoma and chromophobe. Three hundred and fifty-one patients were analyzed: 164 patients with oncocytoma, 28 with oncocytic neoplasms, and 159 with chromophobe tumors. Results Median follow-up time for the entire cohort was 32.4 months, (interquartile range 9.2–70.0). Seventeen total patients (17/351, 4.9%) died during the course of the study. In patients with oncocytoma or oncocytic neoplasm, none were known to metastasize or die of their disease. Only chromophobe tumors >6 cm in size in our series demonstrated metastatic progression and approximately half of these metastasized tumors demonstrated sarcomatoid changes. Conclusion Variant oncocytic neoplasms appear to have a natural course similar to classic oncocytoma. These tumors appear to have no metastatic potential, and oncologic surveillance may not be indicated after surgery

Population III stars and the Long Gamma Ray Burst rate

Because massive, low-metallicity population III (PopIII) stars may produce very powerful long gamma-ray bursts (LGRBs), high-redshift GRB observations could probe the properties of the first stars. We analyze the correlation between early PopIII stars and LGRBs by using cosmological N-body/hydrodynamical simulations, which include detailed chemical evolution, cooling, star formation, feedback effects and the transition between PopIII and more standard population I/II (PopII/I) stars. From the Swift observed rate of LGRBs, we estimate the fraction of black holes that will produce a GRB from PopII/I stars to be in the range 0.028<f_{GRB}<0.140, depending on the assumed upper metallicity of the progenitor. Assuming that as of today no GRB event has been associated to a PopIII star, we estimate the upper limit for the fraction of LGRBs produced by PopIII stars to be in the range 0.006<f_{GRB}<0.022. When we apply a detection threshold compatible with the BAT instrument, we find that the expected fraction of PopIII GRBs (GRB3) is ~10% of the full LGRB population at z>6, becoming as high has 40% at z>10. Finally, we study the properties of the galaxies hosting our sample of GRB3. We find that the average metallicity of the galaxies hosting a GRB3 is typically higher than the critical metallicity used to select the PopIII stars, due to the efficiency in polluting the gas above such low values. We also find that the highest probability of finding a GRB3 is within galaxies with a stellar mass <10^7 Msun, independently from the redshift.Comment: 8 pages,3 figures. Submitted to MNRAS, revised version after referee's comment

Prevalence of Children with Severe Fetal Alcohol Spectrum Disorders in Communities Near Rome, Italy: New Estimated Rates Are Higher than Previous Estimates

Objective: To determine the population-based epidemiology of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) in towns representative of the general population of central Italy. Methods: Slightly revised U.S. Institute of Medicine diagnostic methods were used among children in randomly-selected schools near Rome. Consented first grade children (n = 976) were screened in Tier I for height, weight, or head circumference and all childre

Cosmology at Low Frequencies: The 21 cm Transition and the High-Redshift Universe

Observations of the high-redshift Universe with the 21 cm hyperfine line of neutral hydrogen promise to open an entirely new window onto the early phases of cosmic structure formation. Here we review the physics of the 21 cm transition, focusing on processes relevant at high redshifts, and describe the insights to be gained from such observations. These include measuring the matter power spectrum at z~50, observing the formation of the cosmic web and the first luminous sources, and mapping the reionization of the intergalactic medium. The epoch of reionization is of particular interest, because large HII regions will seed substantial fluctuations in the 21 cm background. We also discuss the experimental challenges involved in detecting this signal, with an emphasis on the Galactic and extragalactic foregrounds. These increase rapidly toward low frequencies and are especially severe for the highest redshift applications. Assuming that these difficulties can be overcome, the redshifted 21 cm line will offer unique insight into the high-redshift Universe, complementing other probes but providing the only direct, three-dimensional view of structure formation from z~200 to z~6.Comment: extended review accepted by Physics Reports, 207 pages, 44 figures (some low resolution); version with high resolution figures available at http://pantheon.yale.edu/~srf28/21cm/index.htm; minor changes to match published versio