Genome-wide Profiling of RNA splicing in prostate tumor from RNA-seq data using virtual microarrays

BACKGROUND: Second generation RNA sequencing technology (RNA-seq) offers the potential to interrogate genome-wide differential RNA splicing in cancer. However, since short RNA reads spanning spliced junctions cannot be mapped contiguously onto to the chromosomes, there is a need for methods to profile splicing from RNA-seq data. Before the invent of RNA-seq technologies, microarrays containing probe sequences representing exon-exon junctions of known genes have been used to hybridize cellular RNAs for measuring context-specific differential splicing. Here, we extend this approach to detect tumor-specific splicing in prostate cancer from a RNA-seq dataset. METHOD: A database, SPEventH, representing probe sequences of under a million non-redundant splice events in human is created with exon-exon junctions of optimized length for use as virtual microarray. SPEventH is used to map tens of millions of reads from matched tumor-normal samples from ten individuals with prostate cancer. Differential counts of reads mapped to each event from tumor and matched normal is used to identify statistically significant tumor-specific splice events in prostate. RESULTS: We find sixty-one (61) splice events that are differentially expressed with a p-value of less than 0.0001 and a fold change of greater than 1.5 in prostate tumor compared to the respective matched normal samples. Interestingly, the only evidence, EST (BF372485), in the public database for one of the tumor-specific splice event joining one of the intron in KLK3 gene to an intron in KLK2, is also derived from prostate tumor-tissue. Also, the 765 events with a p-value of less than 0.001 is shown to cluster all twenty samples in a context-specific fashion with few exceptions stemming from low coverage of samples. CONCLUSIONS: We demonstrate that virtual microarray experiments using a non-redundant database of splice events in human is both efficient and sensitive way to profile genome-wide splicing in biological samples and to detect tumor-specific splicing signatures in datasets from RNA-seq technologies. The signature from the large number of splice events that could cluster tumor and matched-normal samples into two tight separate clusters, suggests that differential splicing is yet another RNA phenotype, alongside gene expression and SNPs, that can be exploited for tumor stratification

Impact of heat stress on expression pattern of nine rice heat shock factor genes and its traits related to tolerance

65-75Global warming is unusually increasing the earth temperature over the past century at an average rate of 0.07 per decade since 1880. The increased temperature exhibit greater impact on grain yield, approximately 5.18 million tons of rice yields due to heat wave. Heat shock factors (HSF) has major role in regulating heat shock proteins which in turn responsible for survival of plants in heat stress by refolding proteins, maintaining functional confirmation, aiding in host defence mechanism. The aim of this research was to analyse phenological, biochemical changes and key genes highly expressed during heat stress at flowering stage in rice. Expression analysis of nine HSF genes had given a differential expression under heat stress as compared to controlled traits. This study suggested OsHSP26.7 as most responsive gene under heat stress and rice line 159, RRF-127, GP-145-103 and Annada with heat tolerant adaptive mechanisms and better performance under high temperatures and was found to be in correlation with the estimated biochemical traits. This can be taken as a base for heat tolerance response of the crop, which may be useful for further validation studies of the candidate genes for heat tolerance in the rice as well as other crop plants

Participatory non-GM cotton breeding to safeguard organic cotton production in India

Due to fast spread of genetically modified (GM) Bt-cotton, organic farmers in India were suddenly exposed to a severe shortage of non-GM seed threatening the organic cotton production. Therefore, organic cotton grower organisations got engaged in decentralized participatory cotton breeding to develop their own locally adapted cultivars and to reintroduce the traditional more robust Desi cotton species. By engaging and training advisors and farmers using participatory methods, they became researchers and breeders. The close collaboration with the textile industry ensures that the market demand is also met. Training of male and female farmers in cultivar selection and seed propagation made them independent from global seed companies. Participatory breeding is an important tool to get prepared for future challenges like climate change and at the same time strengthens the relationship along the value chain. The project can serve as a successful model for other organisations and crops

Molecular mapping of genomic regions harbouring QTLs for root and yield traits in sorghum (Sorghum bicolor L. Moench)

Root system is a vital part of plants for absorbing soil moisture and nutrients and it influences the drought tolerance. Identification of the genomic regions harbouring quantitative trait loci (QTLs) for root and yield traits, and the linked markers can facilitate sorghum improvement through marker-assisted selection (MAS) besides the deeper understanding of the plant response to drought stress. A population of 184 recombinant inbred lines (RILs), derived from E36-1 × SPV570, along with parents were phenotyped for component traits of yield in field and root traits in an above ground rhizotron. High estimates of heritability and genetic advance for all the root traits and for most of the yield traits, presents high scope for improvement of these traits by simple selection. A linkage map constructed with 104 marker loci comprising 50 EST-SSRs, 34 non-genic nuclear SSRs and 20 SNPs, and QTL analysis was performed using composite interval mapping (CIM) approach. A total of eight and 20 QTLs were mapped for root and yield related traits respectively. The QTLs for root volume, root fresh weight and root dry weight were found co-localized on SBI-04, supported by a positive correlation among these traits. Hence, these traits can be improved using the same linked markers. The lack of overlap between the QTLs of component traits of root and yield suggested that these two sets of parameters are independent in their influence and the possibility of combining these two traits might enhance productivity of sorghum under receding moisture condition

Tolerability of breast ductal lavage in women from families at high genetic risk of breast cancer

<p>Abstract</p> <p>Background</p> <p>Ductal lavage (DL) has been proposed as a minimally-invasive, well-tolerated tool for obtaining breast epithelial cells for cytological evaluation of breast cancer risk. We report DL tolerability in <it>BRCA1/2 </it>mutation-positive and -negative women from an IRB-approved research study.</p> <p>Methods</p> <p>165 <it>BRCA1/2 </it>mutation-positive, 26 mutation-negative and 3 mutation unknown women underwent mammography, breast MRI and DL. Psychological well-being and perceptions of pain were obtained before and after DL, and compared with pain experienced during other screening procedures.</p> <p>Results</p> <p>The average <b><it>anticipated </it></b>and <b><it>experienced </it></b>discomfort rating for DL, 47 and 48 (0–100), were significantly higher (<it>p </it>< 0.01) than the <b><it>anticipated </it></b>and <b><it>experienced </it></b>discomfort of mammogram (38 and 34), MRI (36 and 25) or nipple aspiration (42 and 27). Women with greater pre-existing emotional distress experienced more DL-related discomfort than they anticipated. Women reporting DL-related pain as worse than expected were nearly three times more likely to refuse subsequent DL than those reporting it as the same or better than expected. Twenty-five percent of participants refused repeat DL at first annual follow-up.</p> <p>Conclusion</p> <p>DL was anticipated to be and experienced as <b>more </b>uncomfortable than other procedures used in breast cancer screening. Higher underlying psychological distress was associated with decreased DL tolerability.</p

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Integrating transcriptomic and proteomic data for accurate assembly and annotation of genomes

© 2017 Wong et al.; Published by Cold Spring Harbor Laboratory Press. Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly and annotation of newly sequenced genomes. Here, we provide a proof-of-concept of an integrated approach for analysis of the genome and proteome of Anopheles stephensi, which is one of the most important vectors of the malaria parasite. To achieve broad coverage of genes, we carried out transcriptome sequencing and deep proteome profiling of multiple anatomically distinct sites. Based on transcriptomic data alone, we identified and corrected 535 events of incomplete genome assembly involving 1196 scaffolds and 868 protein-coding gene models. This proteogenomic approach enabled us to add 365 genes that were missed during genome annotation and identify 917 gene correction events through discovery of 151 novel exons, 297 protein extensions, 231 exon extensions, 192 novel protein start sites, 19 novel translational frames, 28 events of joining of exons, and 76 events of joining of adjacent genes as a single gene. Incorporation of proteomic evidence allowed us to change the designation of more than 87 predicted noncoding RNAs to conventional mRNAs coded by protein-coding genes. Importantly, extension of the newly corrected genome assemblies and gene models to 15 other newly assembled Anopheline genomes led to the discovery of a large number of apparent discrepancies in assembly and annotation of these genomes. Our data provide a framework for how future genome sequencing efforts should incorporate transcriptomic and proteomic analysis in combination with simultaneous manual curation to achieve near complete assembly and accurate annotation of genomes

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

GWTC-1: A Gravitational-Wave Transient Catalog of Compact Binary Mergers Observed by LIGO and Virgo during the First and Second Observing Runs

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1  M⊙ during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6−0.7+3.2  M⊙ and 84.4−11.1+15.8  M⊙ and range in distance between 320−110+120 and 2840−1360+1400  Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110−3840  Gpc−3 y−1 for binary neutron stars and 9.7−101  Gpc−3 y−1 for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610  Gpc−3 y−1

Properties of the Binary Neutron Star Merger GW170817

On August 17, 2017, the Advanced LIGO and Advanced Virgo gravitational-wave detectors observed a low-mass compact binary inspiral. The initial sky localization of the source of the gravitational-wave signal, GW170817, allowed electromagnetic observatories to identify NGC 4993 as the host galaxy. In this work, we improve initial estimates of the binary's properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data. We extend the range of gravitational-wave frequencies considered down to 23 Hz, compared to 30 Hz in the initial analysis. We also compare results inferred using several signal models, which are more accurate and incorporate additional physical effects as compared to the initial analysis. We improve the localization of the gravitational-wave source to a 90% credible region of 16  deg2. We find tighter constraints on the masses, spins, and tidal parameters, and continue to find no evidence for nonzero component spins. The component masses are inferred to lie between 1.00 and 1.89  M⊙ when allowing for large component spins, and to lie between 1.16 and 1.60  M⊙ (with a total mass 2.73−0.01+0.04  M⊙) when the spins are restricted to be within the range observed in Galactic binary neutron stars. Using a precessing model and allowing for large component spins, we constrain the dimensionless spins of the components to be less than 0.50 for the primary and 0.61 for the secondary. Under minimal assumptions about the nature of the compact objects, our constraints for the tidal deformability parameter Λ are (0,630) when we allow for large component spins, and 300−230+420 (using a 90% highest posterior density interval) when restricting the magnitude of the component spins, ruling out several equation-of-state models at the 90% credible level. Finally, with LIGO and GEO600 data, we use a Bayesian analysis to place upper limits on the amplitude and spectral energy density of a possible postmerger signal