ALBERT

Description: Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of ‘intergenic splicing’. We also explored the implications of these non-pathological fusions in cancer and in evolution.

Description: We propose an approach to extend the isogeometric analysis (IGA) method to solve material interface problems. The development is carried out through incorporating the advantages of the extended finite element method into the standard IGA approach for solving problems with discontinuities. By applying both the XIGA and IGA methods to solve Poisson's equation problem containing weak discontinuities, we demonstrate that the XIGA achieves the optimal convergence rate, whereas the IGA only converges suboptimally. The proposed method is then successfully applied to solve bimaterial and curved material interface problems.

Description: Motivation: Computationally generated non-native protein structure conformations (or decoys) are often used for designing protein folding simulation methods and force fields. However, almost all the decoy sets currently used in literature suffer from uneven root mean square deviation (RMSD) distribution with bias to non-protein like hydrogen-bonding and compactness patterns. Meanwhile, most protein decoy sets are pre-calculated and there is a lack of methods for automated generation of high-quality decoys for any target proteins. Results: We developed a new algorithm, 3DRobot, to create protein structure decoys by free fragment assembly with enhanced hydrogen-bonding and compactness interactions. The method was benchmarked with three widely used decoy sets from ab initio folding and comparative modeling simulations. The decoys generated by 3DRobot are shown to have significantly enhanced diversity and evenness with a continuous distribution in the RMSD space. The new energy terms introduced in 3DRobot improve the hydrogen-bonding network and compactness of decoys, which eliminates the possibility of native structure recognition by trivial potentials. Algorithms that can automatically create such diverse and well-packed non-native conformations from any protein structure should have a broad impact on the development of advanced protein force field and folding simulation methods. Availiablity and implementation: http://zhanglab.ccmb.med.umich.edu/3DRobot/ Contact: jiay@phy.ccnu.edu.cn ; zhng@umich.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Aims With the continuing increase in the impact of human activities on ecosystems, ecologists are increasingly interested in understanding the effects of high temperature on litter decomposition since litter decomposition and the accompanying release of nutrients and carbon dioxide are key processes in ecosystem nutrient cycling and carbon flux. This study was conducted to evaluate the temperature sensitivity of forest litter decomposition and soil enzymes during litter decomposition in subtropical forest in China. Methods Two dominant litter types were chosen from Zijin Mountain in China: Quercus acutissima leaves from a broadleaf forest (BF) and Pinus massoniana needles from a coniferous forest (CF). The litter samples were incubated in soil microcosms at ambient control temperature (20°C) and 10°C warmer. During a 5-month incubation, chemical composition of litter samples, litter mass losses, and related soil enzyme activities were determined. Important Findings Three main results were found: (i) high temperature accelerated decomposition rates of both litter types, and the temperature sensitivities of litter decomposition for BF leaves and that for CF needles are equivalent basically, (ii) high temperature enhanced soil enzyme activities in the two forest types, and the temperature sensitivities of polyphenol oxidase were significantly higher than those of the other soil enzymes and (iii) the temperature sensitivities of nitrate reductase were significantly higher in the CF soil than in the BF soil, while there was no significant difference in the temperature sensitivities of the other soil enzymes between BF and CF. As a long-term consequence, the high-temperature-induced acceleration of litter decomposition rates in these subtropical forests may cause carbon stored belowground to be transferred in the atmosphere, which may alter the balance between carbon uptake and release, and then alter the global carbon cycle in the coming decades.

Description: Based on the Sloan Digital Sky Survey and South Galactic Cap of u -band Sky Survey (SCUSS) early data, we use a star count method to estimate the Galactic structure parameters in an intermediate latitude with 10 180 main-sequence (MS) stars in an absolute magnitude interval of 4 ≤  M r  ≤ 13. We divide the absolute magnitude into five intervals, 4 ≤  M r  〈 5, 5 ≤  M r  〈 6, 6 ≤  M r  〈 8, 8 ≤  M r  〈 10 and 10 ≤  M r  ≤ 13, and estimate the Galactic structure parameters in each absolute magnitude interval to explore their possible variation with the absolute magnitude. Our study shows that the parameters depend on absolute magnitude. For the thin disc, the intrinsic faint MS stars have large local space density and they tend to stay close to the Galactic plane. A plausible explanation is that faint MS stars with long lifetime experience and long gravitational interaction time result in a short scaleheight. However, for the thick disc, the parameters show a complex trend with absolute magnitude, which may imply the complicated original of the thick disc. For the halo, the intrinsic faint MS stars have large local density and small axial ratio, which indicate a flattened inner halo and a more spherical outer halo.

Description: MicroRNAs (miRNAs) are small non-coding RNA molecules, which act as post-transcriptional regulators of gene expression and have been implicated in initiation, progression and treatment outcome of diverse cancers. Single nucleotide polymorphisms (SNPs), as the most common type of genetic variation, also exist in miRNA genes and can lead to alteration in miRNA expression resulting in diverse functional consequences. Emerging studies have evaluated the association of miRNA SNPs with cancer risk, but the results remain inconclusive. To assess the relationship between miRNA SNPs and cancer risk, we performed a meta-analysis of 18 studies involving 20660 subjects for miR-146a rs2910164 polymorphism and 21 studies involving 26,018 subjects for miR-196a2 rs11614913 polymorphism. As for rs2910164, no significant association of cancer risk was found in the overall analysis. In subgroup analysis by cancer type, ethnicity, source of controls and sample size, significant association of cancer risk was mainly found in papillary thyroid carcinoma, primary liver cancer, cervical cancer, Caucasian population and small sample size studies. For rs11614913, significant results were found in all the tested genetic models and T allele or its carriers were associated with decreased cancer risk in overall analysis (T vs. C: OR = 0.888, 95% CI 0.84–0.938; TT+TC vs. CC: OR = 0.897, 95% CI 0.828–0.971). In stratified analysis by cancer type and ethnicity, significant association of cancer risk was observed in breast cancer, lung cancer, colorectal cancer and Asian population, but not in Caucasian population. During further stratified analysis by source of controls and sample size, results similar to those of overall analysis were found in all of the subgroups. Taken together, our results indicated that miR-196a2 rs11614913 T variant probably contribute to decreased susceptibility to cancer. However, limited evidence was found for association of miR-146a rs2910164 with cancer risk, and further well-designed studies with large sample size will be necessary to validate the effect of miR-146a rs2910164 on cancer susceptibility.

Description: Based on Sloan Digital Sky Survey (SDSS) g, r and South Galactic Cap of u-band Sky Survey (SCUSS) u photometry, we develop a photometric calibration for estimating the stellar metallicity from u – g and g – r colours by using the SDSS spectra of 32 542 F- and G-type main-sequence stars, which cover almost 3700 deg 2 in the south Galactic cap. The rms scatter of the photometric metallicity residuals relative to spectrum-based metallicity is 0.14 dex when g – r  〈 0.4, and 0.16 dex when g – r  〉 0.4. Because of the deeper and more accurate magnitude of SCUSS u band, the estimate can be used up to the faint magnitude of g  = 21. This application range of photometric metallicity calibration is wide enough so that it can be used to study metallicity distribution of distant stars. In this study, we select the Sagittarius (Sgr) stream and its neighbouring field halo stars in south Galactic cap to study their metallicity distribution. We find that the Sgr stream at the cylindrical Galactocentric coordinate of R  ~ 19 kpc, | z | ~ 14 kpc exhibits a relative rich metallicity distribution, and the neighbouring field halo stars in our studied fields can be modelled by two-Gaussian model, with peaks, respectively, at [Fe/H] = –1.9 and –1.5.

Description: Based on the LAMOST survey and Sloan Digital Sky Survey, we use low-resolution spectra of 130 043 F/G-type dwarf stars to study the kinematics and metallicity properties of the Galactic disc. Our study shows that the stars with poorer metallicity and larger vertical distance from the Galactic plane tend to have a larger eccentricity and velocity dispersion. After separating the sample stars into likely thin-disc and thick-disc sub-samples, we find that there exists a negative gradient of rotation velocity V with metallicity [Fe/H] for the likely thin-disc sub-sample, and the thick-disc sub-sample exhibits a larger positive gradient of rotation velocity with metallicity. By comparing with model predictions, we consider that the radial migration of stars appears to have influenced the formation of the thin disc. In addition, our results show that the observed thick-disc stellar orbital eccentricity distribution peaks at low eccentricity ( e ~ 0.2) and extends to a high eccentricity ( e ~ 0.8). We compare this result with four thick-disc formation simulation models, which imply that our result is consistent with the gas-rich merger model.

Description: Accurate knowledge of the mutation rate provides a base line for inferring expected rates of evolution, for testing evolutionary hypotheses and for estimation of key parameters. Advances in sequencing technology now permit direct estimates of the mutation rate from sequencing of close relatives. Within insects there have been three prior such estimates, two in nonsocial insects ( Drosophila : 2.8 x 10 – 9 per bp per haploid genome per generation; Heliconius : 2.9 x 10 – 9 ) and one in a social species, the honeybee (3.4 x 10 – 9 ). Might the honeybee’s rate be ~20% higher because it has an exceptionally high recombination rate and recombination may be directly or indirectly mutagenic? To address this possibility, we provide a direct estimate of the mutation rate in the bumblebee ( Bombus terrestris ), this being a close relative of the honeybee but with a much lower recombination rate. We confirm that the crossover rate of the bumblebee is indeed much lower than honeybees (8.7 cM/Mb vs. 37 cM/Mb). Importantly, we find no significant difference in the mutation rates: we estimate for bumblebees a rate of 3.6 x 10 – 9 per haploid genome per generation (95% confidence intervals 2.38 x 10 – 9 and 5.37 x 10 – 9 ) which is just 5% higher than the estimate that of honeybees. Both genomes have approximately one new mutation per haploid genome per generation. While we find evidence for a direct coupling between recombination and mutation (also seen in honeybees), the effect is so weak as to leave almost no footprint on any between-species differences. The similarity in mutation rates suggests an approximate constancy of the mutation rate in insects.