Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions.

Uncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for novel therapeutic opportunities. To our knowledge, no systematic identification and characterization of transcripts encoding nORFs or their translation products in cancer, or in any other physiological process has been performed. We use our curated nORFs database (nORFs.org), together with RNA-Seq data from The Cancer Genome Atlas (TCGA) and Genotype-Expression (GTEx) consortiums, to identify transcripts containing nORFs that are expressed frequently in cancer or matched normal tissue across 22 cancer types. We show nORFs are subject to extensive dysregulation at the transcript level in cancer tissue and that a small subset of nORFs are associated with overall patient survival, suggesting that nORFs may have prognostic value. We also show that nORF products can form protein-like structures with post-translational modifications. Finally, we perform in silico screening for inhibitors against nORF-encoded proteins that are disrupted in stomach and esophageal cancer, showing that they can potentially be targeted by inhibitors. We hope this work will guide and motivate future studies that perform in-depth characterization of nORF functions in cancer and other diseases.

A platform for curated products from novel open reading frames prompts reinterpretation of disease variants.

Recent evidence from proteomics and deep massively parallel sequencing studies have revealed that eukaryotic genomes contain substantial numbers of as-yet-uncharacterized open reading frames (ORFs). We define these uncharacterized ORFs as novel ORFs (nORFs). nORFs in humans are mostly under 100 codons and are found in diverse regions of the genome, including in long noncoding RNAs, pseudogenes, 3' UTRs, 5' UTRs, and alternative reading frames of canonical protein coding exons. There is therefore a pressing need to evaluate the potential functional importance of these unannotated transcripts and proteins in biological pathways and human disease on a larger scale, rather than one at a time. In this study, we outline the creation of a valuable nORFs data set with experimental evidence of translation for the community, use measures of heritability and selection that reveal signals for functional importance, and show the potential implications for functional interpretation of genetic variants in nORFs. Our results indicate that some variants that were previously classified as being benign or of uncertain significance may have to be reinterpreted.

Evaluation of trophic status and its limiting factors in the Renuka Lake of Lesser Himalaya, India.

The present study is to evaluate trophic status and its limiting factors in the Renuka Lake, using surface water samples. The water of the lake is found to be slightly alkaline with pH 8.33-8.70 (avg. 8.61 ± 0.1). The turbidity 4.63-6.62 NTU (avg. 5.48 ± 0.63 NTU) indicated low level of clarity in the lake. The Carlson's index based on the Secchi disc transparency (SD), chlorophyll-a (Chl-a), and total phosphorus (TP) has indicated that the Renuka Lake is turned hyper-eutrophic in status. The correlation coefficient has indicated that most parameters in the lake are contributed by different sources. Factor-1 marked 26.40% variance, which may be due to higher impact of rock weathering than the anthropogenic activities, whereas 18.56% variance shown by factor-2 may be due to natural and anthropogenic activities. However, factor-3 (14.38% variance) inferred that the higher contribution of Chl-a, pH, TDS, NH4+, NO3-, salinity, and SO42- is due to major impacts of the anthropogenic activities. The inverse distance weighting method has indicated spatial interpolation and area of influence of different parameters in the lake. The "nutrient (TP) limited large sized algae" as well as phosphorus is considered as a major limiting factor for increasing productivity and trophic state index. The present study has inferred that the nutrient enrichment should be controlled to restore the Renuka Lake, owing to its social and ecological significances.

A model to predict the function of hypothetical proteins through a nine-point classification scoring schema.

BACKGROUND: Hypothetical proteins [HP] are those that are predicted to be expressed in an organism, but no evidence of their existence is known. In the recent past, annotation and curation efforts have helped overcome the challenge in understanding their diverse functions. Techniques to decipher sequence-structure-function relationship, especially in terms of functional modelling of the HPs have been developed by researchers, but using the features as classifiers for HPs has not been attempted. With the rise in number of annotation strategies, next-generation sequencing methods have provided further understanding the functions of HPs. RESULTS: In our previous work, we developed a six-point classification scoring schema with annotation pertaining to protein family scores, orthology, protein interaction/association studies, bidirectional best BLAST hits, sorting signals, known databases and visualizers which were used to validate protein interactions. In this study, we introduced three more classifiers to our annotation system, viz. pseudogenes linked to HPs, homology modelling and non-coding RNAs associated to HPs. We discuss the challenges and performance of these classifiers using machine learning heuristics with an improved accuracy from Perceptron (81.08 to 97.67), Naive Bayes (54.05 to 96.67), Decision tree J48 (67.57 to 97.00), and SMO_npolyk (59.46 to 96.67). CONCLUSION: With the introduction of three new classification features, the performance of the nine-point classification scoring schema has an improved accuracy to functionally annotate the HPs.

Draft Genome Sequence of the Plant Growth-Promoting Rhizobacterium Pseudomonas protegens Strain BNJ-SS-45, Isolated from Rhizosphere Soil of Wheat (Triticum aestivum).

Here, we present the draft genome sequence of Pseudomonas protegens strain BNJ-SS-45, which was isolated from wheat rhizosphere. The genome is assembled with 7,116,445 bp with a GC content of 63.34% consisting of 32 scaffolds. The genome is useful in prediction of secondary metabolites, particularly rhizoxin, pyoverdine, and bacteriocin.

Draft Genome Sequence of a Fungus (Fusarium tricinctum) Cultured from a Monoisolate Native to the Himalayas.

Here, we report the draft de novo genome sequence assembly of Fusarium tricinctum (strain T6), using IonTorrent sequencing chemistry and an Ion 530 chip ExT kit for sequencing. The genome assembly resulted in 42,732,204 bp from a total 6.62 Gb, with a median read length of 386 bp.

Assessment of Vitamin D in Rheumatoid Arthritis and Its Correlation with Disease Activity.

BACKGROUND: Vitamin D is believed to have an immunomodulatory and anti-inflammatory action, and its deficiency has been linked with several autoimmune disorders, including rheumatoid arthritis (RA). The relationship between the severity of RA and serum levels of Vitamin D is a subject of immense interest and therapeutic implications. MATERIALS AND METHODS: This was a prospective, comparative study conducted on 100 participants, 50 cases of RA and 50 healthy controls, all in the age group of 18-75 years. Serum Vitamin D levels were measured and compared in cases and controls. Vitamin D levels in RA patients were also assessed in different stages of disease activity to assess the correlation between the two. RESULTS: Eighty-four percent patients of RA were Vitamin D deficient versus only 34% of controls. The serum Vitamin D levels were also significantly lower in the RA patients (mean value of 21.05 ± 10.02 ng/ml), as compared to the controls (mean value of 32.87 ± 14.16 ng/ml). There was a significant inverse correlation between serum Vitamin D levels and RA disease activity. The mean serum Vitamin D levels were 35.28 ± 9.0 ng/ml, 33.80 ± 4.1 ng/ml, 22.47 ± 6.18 ng/ml, and 14.21 ± 6.97 ng/ml in the remission, low disease activity, moderate disease activity, and high disease activity groups, respectively. CONCLUSIONS: Vitamin D deficiency is more common in RA patients and may be one of the causes leading to development or worsening of the disease.

Hydrochemistry and water quality of Rewalsar Lake of Lesser Himalaya, Himachal Pradesh, India.

The present research is to study hydrochemistry and water quality of Rewalsar Lake during pre-monsoon, monsoon, and post-monsoon seasons. The Ca2+ and Na+ are observed as the dominant cations from pre- to post-monsoon season. On the other hand, HCO3- and Cl- are observed dominant anions during pre-monsoon and monsoon seasons, whereas HCO3- and SO42- during post-monsoon season. The comparison of alkaline earth metals with alkali metals and total cations (Tz+) has specified that the carbonate weathering is the dominant source of major ions in the water of lake.  The HCO3- is noticed to be mainly originated from carbonate/calcareous minerals during monsoon and post-monsoon, but through silicate minerals during pre-monsoon.  The SO42- in Rewalsar Lake is produced by the dissolution of calcite and dolomite etc. The alkali metals and Cl- in the lake can be attributed to the silicate weathering as well as halite dissolution and anthropogenic activities. Certain other parameters like NO3-, NH4+, F-, and Br- are mainly a result of anthropogenic activities. The alkaline earth metals are found to surpass over alkali metals, whereas weak acid (HCO3-) exceed to strong acid (SO42-). The Piper diagram has shown Ca2+-HCO3- type of water during all the seasons. The water quality index has indicated that the water quality of the lake is unsuitable for drinking from pre- to post-monsoon. Several parameters like salinity index, sodium adsorption ratio, sodium percent, residual sodium carbonate, magnesium hazard etc. have revealed the water of Rewalsar Lake as suitable for irrigation.

8000-year monsoonal record from Himalaya revealing reinforcement of tropical and global climate systems since mid-Holocene.

We provide the first continuous Indian Summer Monsoon (ISM) climate record for the higher Himalayas (Kedarnath, India) by analyzing a 14C-dated peat sequence covering the last ~8000 years, with ~50 years temporal resolution. The ISM variability inferred using various proxies reveal striking similarity with the Greenland ice core (GISP2) temperature record and rapid denitrification changes recorded in the sediments off Peru. The Kedarnath record provides compelling evidence for a reorganization of the global climate system taking place at ~5.5 ka BP possibly after sea level stabilization and the advent of inter-annual climate variability governed by the modern ENSO phenomenon. The ISM record also captures warm-wet and cold-dry conditions during the Medieval Climate Anomaly and Little Ice Age, respectively.

ExcellmiRDB for translational genomics: a curated online resource for extracellular microRNAs.

A large number of studies have suggested extracellular microRNAs (microRNAs in biofluids) as potential noninvasive biomarkers for pathophysiological conditions such as cancer. However, reported differentially expressed signatures of extracellular miRNAs in diseases are not uniformly consistent among studies. Here, we present "ExcellmiRDB", a curated online database that provides integrated information about miRNAs levels in biofluids in a user-friendly way. Although many miRNA databases, including disease-oriented databases, have been launched before, the ExcellmiRDB is so far the only one specialized for storing curated data on miRNA levels in biofluid samples. At present, ExcellmiRDB has 2773 disease-extracellular miRNAs and 1108 biofluid-extracellular miRNAs relationships curated from 108 articles selected from more than 600 surveyed PubMed abstracts. Information about 992 miRNAs, 82 diseases, 21 biofluids, 8 species, 63 normalization reference genes, 5 techniques, 14 GEO profiles accession numbers, 7 human ethnic groups, and 18 compared clinical biomarkers have been provided in the database. A user can query ExcellmiRDB by selecting a disease or a miRNA or a biofluid. Additionally, the database provides two online network graphs to visualize and interact with the content of the database. The first network shows disease-extracellular miRNAs relationships, along with expression patterns and number of articles for a relationship. The second network visualizes biofluid-extracellular miRNAs relationships showing miRNAs spectrum across different types of biofluids. In conclusion, ExcellmiRDB is a new innovative resource for both academic and industrial researchers in translational omics who are developing miRNA biomarkers for noninvasive diagnostic or prognostic technologies. ExcellmiRDB is publicly available on www.excellmirdb.brfjaisalmer.com/.