Variant peptides resulting from single nucleotide polymorphisms (SNPs) can lead to aberrant protein functions and have translational potential for disease diagnosis and personalized therapy. Variant ...peptides detected by proteogenomics are fraught with high number of false positives, but there is no uniform and comprehensive approach to assess variant quality across analysis pipelines. Despite class-specific FDR along with ad-hoc filters, the problem is far from solved. These protocols are typically manual and tedious, and thus not uniform across labs. We demonstrate that variant peptide rescoring, integrated with intensity, variant event information and search result features, allows better discrimination of correct variant peptides. Implemented into PgxSAVy - a tool for quality control of variant peptides, this method can tackle the high rate of false positives. PgxSAVy provides a rigorous framework for quality control and annotations of variant peptides on the basis of (i) variant quality, (ii) isobaric masses, and (iii) disease annotation. PgxSAVy demonstrated high accuracy by identifying true variants with 98.43% accuracy on simulated data. Large-scale proteogenomic reanalysis of ∼2.8 million spectra (PXD004010 and PXD001468) resulted in 12,705 variant peptide spectrum matches (PSMs), of which PgxSAVy evaluated 3028 (23.8%), 1409 (11.1%) and 8268 (65.1%) as confident, semi-confident and doubtful respectively. PgxSAVy also annotates the variants based on their pathogenicity and provides support for assisted manual validation. The analysis of proteins carrying variants can provide fine granularity in discovering important pathways. PgxSAVy will advance personalized medicine by providing a comprehensive framework for quality control and prioritization of proteogenomics variants. PgxSAVy is freely available at https://pgxsavy.igib.res.in/ as a webserver and https://github.com/anuragraj/PgxSAVy as a stand-alone tool.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fusion transcripts can contribute to diversity of molecular networks in the human cortex. In this study, we explored the occurrence of fusion transcripts in normal human cortex along with single ...neurons and astrocytes. We identified 1305 non-redundant fusion events from 388 transcriptomes representing 59 human cortices and 329 single cells. Our results indicate while the majority of fusion transcripts in human cortex are intra-chromosomal (85%), events found in single neurons and astrocytes were primarily inter-chromosomal (80%). The number of fusions in single neurons was significantly higher than that in single astrocytes (p < 0.05), indicating fusion as a possible contributor towards transcriptome diversity in neuronal cells. The identified fusions were largely private and 4 specific recurring events were found both in cortex and in single neurons but not in astrocytes. We found a significant increase in the number of fusion transcripts in human brain with increasing age both in single cells and whole cortex (p < 0.0005 and < 0.005, respectively). This is likely one of the many possible contributors for the inherent plasticity of the adult brain. The fusion transcripts in fetal brain were enriched for genes for long-term depression; while those in adult brain involved genes enriched for long-term potentiation pathways. Our findings demonstrate fusion transcripts are naturally occurring phenomenon spanning across the health-disease continuum, and likely contribute to the diverse molecular network of human brain.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Lipid compositions of cells, tissues, and bio-fluids are complex, with varying concentrations and structural diversity making their identification challenging. Newer methods for comprehensive ...analysis of lipids are thus necessary. Herein, we propose a targeted-mass spectrometry based lipidomics screening method using a combination of variable retention time window and relative dwell time weightage. Using this method, we identified more than 1000 lipid species within 24-min. The limit of detection varied from the femtomolar to the nanomolar range. About 883 lipid species were detected with a coefficient of variance <30%. We used this method to identify plasma lipids altered due to vitamin B12 deficiency and found a total of 18 lipid species to be altered. Some of the lipid species with ω-6 fatty acid chains were found to be significantly increased while ω-3 decreased in vitamin B12 deficient samples. This method enables rapid screening of a large number of lipid species in a single experiment and would substantially advance our understanding of the role of lipids in biological processes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Geographic routing scheme (such as Greedy perimeter stateless routing) makes use of location information to forward packets greedily. Nodes need to keep only this location information in stateless ...routing. When the greedy forwarding fails, routing switches to perimeter forwarding based on either planar graph (GG and RNG) or cross link detection protocol approaches. However, it has drawback in terms of cost and computational overheads. We propose a coverage-tree heuristic based routing instead of face routing in geographic routing schemes when greedy forwarding fails. We prove that the coverage tree based routing problem is NP hard by reduction using minimum rooted spanning tree of depth 2 (RST 2). We also show that coverage-tree based geographic routing problem is APX hard and not approximable with a factor of
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Proteogenomics refers to the integrated analysis of the genome and proteome that leverages mass-spectrometry (MS)-based proteomics data to improve genome annotations, understand gene ...expression control through proteoforms and find sequence variants to develop novel insights for disease classification and therapeutic strategies. However, proteogenomic studies often suffer from reduced sensitivity and specificity due to inflated database size. To control the error rates, proteogenomics depends on the target-decoy search strategy, the de-facto method for false discovery rate (FDR) estimation in proteomics. The proteogenomic databases constructed from three- or six-frame nucleotide database translation not only increase the search space and compute-time but also violate the equivalence of target and decoy databases. These searches result in poorer separation between target and decoy scores, leading to stringent FDR thresholds. Understanding these factors and applying modified strategies such as two-pass database search or peptide-class-specific FDR can result in a better interpretation of MS data without introducing additional statistical biases. Based on these considerations, a user can interpret the proteogenomics results appropriately and control false positives and negatives in a more informed manner. In this review, first, we briefly discuss the proteogenomic workflows and limitations in database construction, followed by various considerations that can influence potential novel discoveries in a proteogenomic study. We conclude with suggestions to counter these challenges for better proteogenomic data interpretation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Chronic mucous hypersecretion (CMH or chronic bronchitis) per se or when associated with chronic inflammatory airway diseases such as asthma or chronic obstructive pulmonary disease ...(COPD) has several adverse clinical consequences. The sputum fluid phase has several candidate proteins including mucins which have the potential of being therapeutic targets, but has not yet been explored in-depth. This study aimed at exploring the profile of sputum proteins in various airway diseases. Methods: Sputum from thirty-one patients with various airway diseases was collected and the fluid phase analyzed by LC-MS/MS and subsequently by sequential window acquisition of all theoretical fragments ion spectra (SWATH) (n = 15) for protein quantitation. Hierarchical clustering and functional grouping were performed. Results: A total of 185 proteins were quantitated by SWATH of which 21 proteins were identified which could distinguish between the clinical phenotypes by hierarchical clustering. Functional protein clustering revealed 4 groups: those that are inflammation related, oxidative stress related, mucin related and a cytoskeletal and calcium related group. The levels of eight proteins (Azurocidin1, Neutrophil defensin 3, Lactotransferrin, Calmodulin 3, Coronin1A, Mucin 5B, Mucin 5AC and BPI fold containing family B1) were significantly altered (relative to mean) in exacerbator prone subjects compared to nonexacerbators. Another simple but useful metric which emerged from this study was total protein concentration in sputum which was significantly higher in frequent exacerbators. Conclusion: Sputum proteins can detect the various airway disease clinical phenotypes. Total protein concentration and eight other proteins are biomarkers for frequent exacerbators. The clinical and therapeutic implications of the functional groups of proteins need further evaluation. Keywords: proteomics, chronic bronchitis, asthma, COPD, mucin, phenotyping
Metal packaging takes hold Raj, Anurag
Aluminium international today,
01/2023, Volume:
36, Issue:
1
Journal Article
Increased recycled aluminium demand has led to new aluminium-rolling capacity in the US to supply the growing metal packaging industry. For instance, Novelis Inc recently broke ground and began ...construction on its $2.5 billion recycling and rolling plant in Bay Minette AL. Steel Dynamics Inc announced plans to build a recycled aluminium flat-rolled mill in Columbus MS. The strong global aluminium packaging recycling rates drive the increased recycling capacity. According to Ball Corp, the global recycling rate for aluminium beverage cans stands at 70%. Increasingly, leading industry bodies are establishing greater recycling goals. In fact, European Aluminium and Metal Packaging Europe launched a joint roadmap towards achieving 100% aluminium beverage can recycling by 2030. Comparatively, plastic packaging's recycling rate stands at 8.7%, a statistic published by the Environmental Protection Agency and last updated for 2018. Compared to aluminium, plastic bottles, jars and other similar hard-to-collect, sort and recycle articles have a much lower recycling rate. Overall, aluminium's homogenous material enables better recycling than plastics' multi-layered and varied packaging.
Introduction: Idiopathic frozen shoulder (IFS) is a common chronic and disabling condition of shoulder pain characterized by progressive loss of active and passive range of motion (ROM) with unclear ...pathogenesis. The ideal treatment protocol is still controversial but commonly used treatment includes single agent or combination of oral non-steroid anti- inflammatory drugs (NSAIDS), oral steroids, intra-articular steroid injection and physiotherapy.
Objective: The objective of this study was to evaluate the effectiveness of intra-articular methylprednisolone injection for pain and ROM in patients suffering from idiopathic frozen shoulder who did not respond to oral NSAIDS with or without oral steroid.
Methodology: A total of 70 patients suffering from IFS were enrolled in this cross sectional study from May 2017–October 2018 from outpatient department of orthopaedic and physiotherapy of Koshi Zonal Hospital. All the patients underwent treatment protocol that comprised of Intra-articular steroid injection followed by five days of oral NSAIDS along with five days regime of physical therapy at the physiotherapy centre, followed by home exercise program. Each patient was followed up at every two weeks interval from intra-articular injection till 6th week. Each patient was evaluated for range of motion (ROM), Numerical Pain Rating Scale (NPRS) and Shoulder Pain and Disability Index (SPADI) before the treatment protocol and at every follow up visit. Data was analyzed using Microsoft Excel Program.
Results: All patients enrolled for the study had satisfactory response. The mean age of the patient was 51.8 years (range 40-65 years). The mean age of the 26 male patients was 54 years (range 45-65), whereas the mean age of 44 female patients was 50.5 years (range 45-60). Mean duration of illness was 26.5 weeks (range 18-32 weeks), SPADI before medication was 83.14, at 2nd week was 50.92, at 4th week was 38.63 and at 6th week was 27.22.
Conclusion: Combination of intra-articular methylprednisolone injection, physiotherapy and home exercise program is effective in IFS for rapid improvement in pain and ROM.
Introduction: Distal femoral fractures comprise 4-6% of all femur fractures. The management of distal femur fractures are challenging because of significant morbidity and complication rate even with ...advanced surgical techniques and implants. Open reduction and internal fixation (ORIF) with pre-contoured distal femoral locking compression plate (DF-LCP) is one of the most acceptable surgical procedures these days.Objectiv: Evaluation of functional outcomes of distal femur fractures managed surgically using DF-LCP at Koshi Zonal Hospital.Methodology: In this cross sectional study 21 patients having closed distal femur fractures with or without intra-articular extension to femoral condyle fixed with DF-LCP at Koshi Zonal Hospital, Nepal from March 2016 to March 2017 were included. Patients with open fracture, severe comminuted fracture, and neurovascular impairment were excluded. These patients were followed-up for up to one year and we recorded the knee range of motion, full weight bearing time fracture union time, and complications. We used Neers' functional scoring system to evaluate the final outcomes and data was analysed using Microsoft Excel Programe.Results: Out of the 21 patients of distal femur fractures, 16 were diametaphyseal distal femur fractures and five were supracondylar fractures with intra-articular extension. Mean age recorded was 45 (range 19-75) years, hospital stay mean duration 12 (range 10-19) days and duration of surgery 85 (range 60-150) minutes, full weight bearing walking time mean 16 (range 12-22) weeks, radiological union time mean 20 (range 17-29) weeks and Neers' score was excellent in 66.66%, satisfactory in 23.80%, unsatisfactory in 4.76%, and poor in 4.76%.None of our patients had complications like; loss of fixation, implant failure or post-operative neurovascular injury.Conclusion: Distal Femoral Locking Plate is one of the best implant to be used as fixation method for both extra-articular and intraarticular distal femur fracture.Birat Journal of Health SciencesVol.2/No.3/Issue 4/Sep- Dec 2017, Page: 260-265
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