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2.
Arch Orthop Trauma Surg ; 144(3): 1311-1330, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37979098

ABSTRACT

INTRODUCTION: Total knee arthroplasty (TKA) can be performed with either conventional off-the-shelf (OTS) or customized individually-made (CIM) implants. The evidence for CIM implants is limited and variable, and the aim of this review was to compare clinical and radiological outcomes between CIM and OTS implants. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Studies reporting on clinical, radiological, or alignment outcomes for CIM and OTS implants were selected. The studies were appraised using the Methodical index for non-randomized studies tool. RESULTS: Twenty-three studies fulfilled the inclusion criteria. The studies comprised 2856 CIM and 1877 OTS TKAs. Revision rate was higher with CIM (5.9%) compared to OTS (3.7%) implants [OR 1.23(95% CI 0.69-2.18)]. Manipulation under anesthesia (MUA) was higher in CIM (2.2%) compared to OTS (1.1%) group [OR 2.95(95% CI 0.95-9.13)] and complications rate was higher in CIM (5%) vs. OTS (4.5%) [OR 1.45(95% CI 0.53-3.96)] but neither reached statistical significance. Length of stay was significantly shorter in CIM group 2.9 days vs. 3.5 days [MD - 0.51(95% CI - 0.82 to - 0.20)]. Knee Society Score showed no difference between CIM and OTS groups for Knee 90.5 vs. 90.6 [MD - 0.27(95% CI - 4.27 to 3.73)] and Function 86.1 vs. 83.1 [MD 1.51(95% CI - 3.69 to 6.70)]. CONCLUSION: CIM implants in TKA have theoretical benefits over OTS prostheses. However, in this present review, CIM implants were associated with higher revisions, MUA, and overall complication rates. There was no difference in outcome score and CIM implants did not improve overall target alignment; however, more CIM TKAs were found to be in the HKA target zone compared to OTS TKAs. The findings of this review do not support the general utilization of CIM over OTS implants in TKA.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Osteoarthritis, Knee , Humans , Knee Joint/surgery , Knee/surgery , Osteoarthritis, Knee/surgery , Treatment Outcome
3.
Orthop Traumatol Surg Res ; 109(4): 103424, 2023 06.
Article in English | MEDLINE | ID: mdl-36182090

ABSTRACT

INTRODUCTION: Posterior shoulder instability (PSI) is a rare and challenging pathology to manage. The aim of this review was to assess and compare whether open and arthroscopic iliac crest bone graft (ICBG) bone block procedures succeeded in improving functional and clinical outcomes as well as radiological outcomes of union and graft resorption. HYPOTHESIS: We hypothesised that there will be no difference in recurrence rate and functional outcome between open and arthroscopic procedures but there will be a higher complication rate with open bone block procedures. METHODS: A systematic review was conducted in accordance with PRISMA guidelines using the online databases MEDLINE and Embase. The review was registered on the PROSPERO database. Studies of open or arthroscopic ICBG bone block procedures reporting patient reported outcome measures, recurrence, complications and progression to osteoarthritis and radiological outcomes of graft union and resorption were selected. Studies were appraised using the Methodical index for non-randomised studies (MINORS) tool. RESULTS: 14 studies satisfied the inclusion criteria; five studies were arthroscopic and nine used open techniques. A total of 183 patients and 201 shoulders were included, mean age was 25 years range (14-75 years). Recurrent instability ranged from 0% to 12.5% for arthroscopic and 0% to 36.4% for open studies. Arthroscopic studies had statistically significant increases in numerous functional outcome scores but there was no evidence for similar improvements in open studies. Osteoarthritis at follow-up ranged from 12.5% to 47% in arthroscopic and 0% to 81.8% for open studies. Arthroscopic complication rate ranged from 6.7% to 75% compared to 0% to 80% for open studies. Majority of complications were metalware related requiring surgical intervention. Partial graft resorption ranged from 7.7-100% after arthroscopic and 4.8-100% after open procedures. High union rates were seen with both open and arthroscopic techniques. CONCLUSION: This study highlights a lack of high-level evidence for arthroscopic and open posterior bone block procedures using ICBG to manage PSI. Functional and instability outcome scores showed significant improvement with arthroscopic ICBG bone block procedures however limited evidence was available for open studies. Metalwork related complications requiring revision and radiographic progression to osteoarthritis was high in both arthroscopic and open studies. LEVEL OF EVIDENCE: IV, systematic review.


Subject(s)
Joint Instability , Osteoarthritis , Shoulder Dislocation , Shoulder Joint , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Shoulder , Joint Instability/diagnostic imaging , Joint Instability/surgery , Shoulder Joint/surgery , Ilium/transplantation , Autografts , Arthroscopy/methods , Shoulder Dislocation/surgery , Osteoarthritis/diagnostic imaging , Osteoarthritis/surgery , Recurrence
4.
BMJ Open ; 12(5): e057148, 2022 05 13.
Article in English | MEDLINE | ID: mdl-35568488

ABSTRACT

INTRODUCTION: The number of people living with and beyond cancer is increasing rapidly. Many of them will experience ongoing physical or psychological sequelae as a result of their original cancer diagnosis or comorbidities arising from risk factors common to cancers and other long-term conditions. This poses the complex problem of managing cancer as a 'chronic' illness along with other existing comorbidities. This scoping review aims to map the literature available on multimorbidity in patients living with and beyond cancer, to explore, quantify and understand the impact of comorbid illnesses to inform work around cancer care in UK primary care settings. METHODS AND ANALYSIS: This review will be guided by Joanna Briggs Institute Reviewer's manual for scoping reviews. A systematic literature search using Medical Subject Heading and text words related to cancer survivors and multimorbidity will be performed in MEDLINE, CINAHL, Embase and Web of Science, from 1990. Results will be described in a narrative style, reported in extraction tables and diagrams, and where appropriate in themes and text. ETHICS AND DISSEMINATION: The scoping review will undertake secondary analysis of published literature; therefore, ethics committee approval is not required. Results will be disseminated through a peer-reviewed scientific journal and presented in relevant conferences. The scoping review will inform understanding of the burden of multimorbidity for cancer survivors, thus allow families, practitioners, clinicians and researchers to take the steps necessary to improve patient-centred care.


Subject(s)
Cancer Survivors , Neoplasms , Chronic Disease , Comorbidity , Humans , Multimorbidity , Neoplasms/epidemiology , Neoplasms/therapy , Research Design , Review Literature as Topic
5.
Cancers (Basel) ; 15(1)2022 Dec 31.
Article in English | MEDLINE | ID: mdl-36612275

ABSTRACT

The study aimed to develop a prediction model for differentiating suspected PDAC from benign conditions. We used a prospective cohort of patients with pancreatic disease (n = 762) enrolled at the Barts Pancreas Tissue Bank (2008-2021) and performed a case-control study examining the association of PDAC (n = 340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Age (over 55), weight loss in hypertensive patients, recent symptoms of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low red blood cell count and low serum sodium were identified as the most important features. These predictors were then used for training several machine-learning-based risk-prediction models on 75% of the cohort. Models were assessed on the remaining 25%. A logistic regression-based model had the best overall performance in the validation cohort (area-under-the-curve = 0.90; Spiegelhalter's z = -1·82, p = 0.07). Setting a probability threshold of 0.15 guided by the maximum F2-score of 0.855, 96.8% sensitivity was reached in the full cohort, which could lead to earlier detection of 84.7% of the PDAC patients. The prediction model has the potential to be applied in primary, secondary and emergency care settings for the early distinction of suspected PDAC patients and expedited referral to specialist hepato-pancreatico-biliary services.

6.
BMC Cancer ; 21(1): 1279, 2021 Nov 27.
Article in English | MEDLINE | ID: mdl-34837975

ABSTRACT

BACKGROUND: Pancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics. METHODS: We conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models. RESULTS: We observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer. CONCLUSIONS: Several factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives.


Subject(s)
Alcohol Drinking , Electronic Health Records , Pancreatic Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Alcohol Drinking/epidemiology , Chronic Disease , Comorbidity , Diabetes Mellitus/epidemiology , Epidemiologic Methods , Ethnicity , Female , Hernia, Abdominal/epidemiology , Humans , Life Style , London/epidemiology , London/ethnology , Male , Middle Aged , Pancreatic Diseases/epidemiology , Pancreatic Neoplasms/ethnology , Pancreatic Neoplasms/mortality , Risk Factors , Smoking/epidemiology , Young Adult
7.
Front Immunol ; 12: 723566, 2021.
Article in English | MEDLINE | ID: mdl-34504498

ABSTRACT

There is a pressing need for novel immunotherapeutic targets in colorectal cancer (CRC). Cytotoxic T cell infiltration is well established as a key prognostic indicator in CRC, and it is known that these tumor infiltrating lymphocytes (TILs) target and kill tumor cells. However, the specific antigens that drive these CD8+ T cell responses have not been well characterized. Recently, phosphopeptides have emerged as strong candidates for tumor-specific antigens, as dysregulated signaling in cancer leads to increased and aberrant protein phosphorylation. Here, we identify 120 HLA-I phosphopeptides from primary CRC tumors, CRC liver metastases and CRC cell lines using mass spectrometry and assess the tumor-resident immunity against these posttranslationally modified tumor antigens. Several CRC tumor-specific phosphopeptides were presented by multiple patients' tumors in our cohort (21% to 40%), and many have previously been identified on other malignancies (58% of HLA-A*02 CRC phosphopeptides). These shared antigens derived from mitogenic signaling pathways, including p53, Wnt and MAPK, and are therefore markers of malignancy. The identification of public tumor antigens will allow for the development of broadly applicable targeted therapeutics. Through analysis of TIL cytokine responses to these phosphopeptides, we have established that they are already playing a key role in tumor-resident immunity. Multifunctional CD8+ TILs from primary and metastatic tumors recognized the HLA-I phosphopeptides presented by their originating tumor. Furthermore, TILs taken from other CRC patients' tumors targeted two of these phosphopeptides. In another cohort of CRC patients, the same HLA-I phosphopeptides induced higher peripheral T cell responses than they did in healthy donors, suggesting that these immune responses are specifically activated in CRC patients. Collectively, these results establish HLA-I phosphopeptides as targets of the tumor-resident immunity in CRC, and highlight their potential as candidates for future immunotherapeutic strategies.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Colorectal Neoplasms/immunology , Histocompatibility Antigens Class I/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Phosphopeptides/immunology , Cell Line, Tumor , Humans , T-Lymphocytes, Cytotoxic/immunology
8.
BMJ Open ; 11(4): e045077, 2021 04 19.
Article in English | MEDLINE | ID: mdl-33875444

ABSTRACT

OBJECTIVE: To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions. DESIGN: Cross-sectional study. SETTING: East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020. PARTICIPANTS: EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background. MAIN OUTCOME MEASURE: COVID-19 incidence and mortality. RESULTS: Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19). CONCLUSIONS: In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.


Subject(s)
COVID-19/complications , Liver Diseases , Pancreatic Diseases , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Cross-Sectional Studies , Female , Humans , Liver Diseases/epidemiology , London/epidemiology , Male , Middle Aged , Pancreatic Diseases/epidemiology , Risk Factors , State Medicine , Young Adult
9.
Preprint in English | medRxiv | ID: ppmedrxiv-20189621

ABSTRACT

ObjectiveTo explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions. DesignCross-sectional study. SettingEast London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) study at Barts Health NHS Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age [≥] 18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020. ParticipantsEL-PaC-Epidem study participants, alive on 12 February 2020, and living in East London within the previous six months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background. Main outcome measureCOVID-19 incidence and mortality. ResultsSome 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with an increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance mis-users were at more risk of infection, so were patients on Vitamin D treatment. The higher odds ratios in patients with chronic pancreatic or mild liver conditions, age>70, and history of smoking or obesity were due to co-existing comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19). ConclusionsIn this large population-based study of HPB patients, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multi-morbidities, substance mis-use, and a history of Vitamin D treatment independently posed higher odds of acquiring COVID-19 compared to their respective counterparts. The odds of death were significantly high for men and Black people. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIFirst multi-ethnic population-based study on COVID-19 in patients with hepato-pancreato-biliary group of diseases. C_LIO_LISystematic identification of the effect, or the lack of it, of individual demographic and clinical factors on the infection and mortality of COVID-19 in a large cohort of over 15 000 patients, robustly controlling for potential confounders in their evaluation. C_LIO_LIAccess to longitudinal data from linked primary and secondary care electronic health records, and use of rule-based phenotyping algorithms allowed for improved completeness and accuracy of the explored variables. C_LIO_LISome observed increased odds of SARS-CoV-2 infection and related death could be plausibly explained by unmeasured confounding. C_LIO_LIThe effects reported in the study could be influenced by the relatively smaller size of COVID-19 cases within this cohort. C_LI

10.
Nucleic Acids Res ; 48(W1): W185-W192, 2020 07 02.
Article in English | MEDLINE | ID: mdl-32496546

ABSTRACT

SNPnexus is a web-based annotation tool for the analysis and interpretation of both known and novel sequencing variations. Since its last release, SNPnexus has received continual updates to expand the range and depth of annotations provided. SNPnexus has undergone a complete overhaul of the underlying infrastructure to accommodate faster computational times. The scope for data annotation has been substantially expanded to enhance biological interpretations of queried variants. This includes the addition of pathway analysis for the identification of enriched biological pathways and molecular processes. We have further expanded the range of user directed annotation fields available for the study of cancer sequencing data. These new additions facilitate investigations into cancer driver variants and targetable molecular alterations within input datasets. New user directed filtering options have been coupled with the addition of interactive graphical and visualization tools. These improvements streamline the analysis of variants derived from large sequencing datasets for the identification of biologically and clinically significant subsets in the data. SNPnexus is the most comprehensible web-based application currently available and these new set of updates ensures that it remains a state-of-the-art tool for researchers. SNPnexus is freely available at https://www.snp-nexus.org.


Subject(s)
Genetic Variation , Genome, Human , Molecular Sequence Annotation , Software , Humans , Internet , Neoplasms/genetics
11.
Environ Sci Technol ; 53(22): 13126-13135, 2019 Nov 19.
Article in English | MEDLINE | ID: mdl-31657213

ABSTRACT

Goethite (α-FeOOH) is dispersed throughout the earth's surface, and its propensity to recrystallize in aqueous solutions determines whether this mineral is a source or sink for critical trace elements in the environment. Under reducing conditions, goethite commonly coexists with aqueous Fe(II) (Fe(II)aq), which accelerates recrystallization by coupled electron transfer and atom exchange. Quantifying the amount of the mineral phase that exchanges its structural Fe(III) atoms with Fe(II)aq is complicated by recrystallization models with untested assumptions of whether, and to what extent, the recrystallized portion of the mineral continues to interact with the solution. Here, we reacted nanoparticulate goethite with 57Fe-enriched Fe(II)aq and used atom probe tomography (APT) to resolve the three-dimensional distribution of Fe isotopes in goethite at the sub nm scale. We found that the 57Fe tracer isotope is enriched in the bulk structure (tens of nanometers deep), with some samples having 57Fe penetration throughout at a level that is similar to the isotopic composition of Fe(II)aq. This suggests that some particles undergo near-complete recrystallization. In other cases, however, the distribution of 57Fe is more heterogeneous and generally concentrates near the particle periphery. Nanoparticle encapsulation and subsequent APT can hence capture hidden recrystallization mechanisms which are critical to predicting mineral reactivity in aqueous solutions.


Subject(s)
Iron Compounds , Trace Elements , Ferric Compounds , Minerals , Oxidation-Reduction
12.
Brief Bioinform ; 20(1): 130-143, 2019 01 18.
Article in English | MEDLINE | ID: mdl-28981577

ABSTRACT

Innovations in -omics technologies have driven advances in biomedical research. However, integrating and analysing the large volumes of data generated from different high-throughput -omics technologies remain a significant challenge to basic and clinical scientists without bioinformatics skills or access to bioinformatics support. To address this demand, we have significantly updated our previous O-miner analytical suite, to incorporate several new features and data types to provide an efficient and easy-to-use Web tool for the automated analysis of data from '-omics' technologies. Created from a biologist's perspective, this tool allows for the automated analysis of large and complex transcriptomic, genomic and methylomic data sets, together with biological/clinical information, to identify significantly altered pathways and prioritize novel biomarkers/targets for biological validation. Our resource can be used to analyse both in-house data and the huge amount of publicly available information from array and sequencing platforms. Multiple data sets can be easily combined, allowing for meta-analyses. Here, we describe the analytical pipelines currently available in O-miner and present examples of use to demonstrate its utility and relevance in maximizing research output. O-miner Web server is free to use and is available at http://www.o-miner.org.


Subject(s)
Data Analysis , Genomics/statistics & numerical data , Software , Computational Biology , DNA Methylation , Databases, Genetic/statistics & numerical data , Gene Dosage , Gene Expression Profiling/statistics & numerical data , Humans , Internet , Neoplasms/genetics , Sequence Analysis, RNA/statistics & numerical data , Software Design , Whole Genome Sequencing/statistics & numerical data
13.
Nucleic Acids Res ; 46(W1): W109-W113, 2018 07 02.
Article in English | MEDLINE | ID: mdl-29757393

ABSTRACT

Broader functional annotation of genetic variation is a valuable means for prioritising phenotypically-important variants in further disease studies and large-scale genotyping projects. We developed SNPnexus to meet this need by assessing the potential significance of known and novel SNPs on the major transcriptome, proteome, regulatory and structural variation models. Since its previous release in 2012, we have made significant improvements to the annotation categories and updated the query and data viewing systems. The most notable changes include broader functional annotation of noncoding variants and expanding annotations to the most recent human genome assembly GRCh38/hg38. SNPnexus has now integrated rich resources from ENCODE and Roadmap Epigenomics Consortium to map and annotate the noncoding variants onto different classes of regulatory regions and noncoding RNAs as well as providing their predicted functional impact from eight popular non-coding variant scoring algorithms and computational methods. A novel functionality offered now is the support for neo-epitope predictions from leading tools to facilitate its use in immunotherapeutic applications. These updates to SNPnexus are in preparation for its future expansion towards a fully comprehensive computational workflow for disease-associated variant prioritization from sequencing data, placing its users at the forefront of translational research. SNPnexus is freely available at http://www.snp-nexus.org.


Subject(s)
Genome, Human/genetics , Polymorphism, Single Nucleotide/genetics , Software , Algorithms , Databases, Genetic , Humans , Internet , Molecular Sequence Annotation , Precision Medicine/trends , RNA, Untranslated/genetics
14.
Nucleic Acids Res ; 46(8): e47, 2018 05 04.
Article in English | MEDLINE | ID: mdl-29390075

ABSTRACT

The vast majority of germline and somatic variations occur in the noncoding part of the genome, only a small fraction of which are believed to be functional. From the tens of thousands of noncoding variations detectable in each genome, identifying and prioritizing driver candidates with putative functional significance is challenging. To address this, we implemented IW-Scoring, a new Integrative Weighted Scoring model to annotate and prioritise functionally relevant noncoding variations. We evaluate 11 scoring methods, and apply an unsupervised spectral approach for subsequent selective integration into two linear weighted functional scoring schemas for known and novel variations. IW-Scoring produces stable high-quality performance as the best predictors for three independent data sets. We demonstrate the robustness of IW-Scoring in identifying recurrent functional mutations in the TERT promoter, as well as disease SNPs in proximity to consensus motifs and with gene regulatory effects. Using follicular lymphoma as a paradigmatic cancer model, we apply IW-Scoring to locate 11 recurrently mutated noncoding regions in 14 follicular lymphoma genomes, and validate 9 of these regions in an extension cohort, including the promoter and enhancer regions of PAX5. Overall, IW-Scoring demonstrates greater versatility in identifying trait- and disease-associated noncoding variants. Scores from IW-Scoring as well as other methods are freely available from http://www.snp-nexus.org/IW-Scoring/.


Subject(s)
DNA, Intergenic/genetics , Genetic Variation , Regulatory Sequences, Nucleic Acid , Computational Biology/methods , Databases, Nucleic Acid/statistics & numerical data , Genome, Human , Genome-Wide Association Study/statistics & numerical data , Humans , Lymphoma, Follicular/genetics , Models, Genetic , Mutation , Neoplasms/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Telomerase/genetics , Whole Genome Sequencing/statistics & numerical data
15.
Nucleic Acids Res ; 46(D1): D1107-D1110, 2018 01 04.
Article in English | MEDLINE | ID: mdl-29059374

ABSTRACT

The Pancreatic Expression Database (PED, http://www.pancreasexpression.org) continues to be a major resource for mining pancreatic -omics data a decade after its initial release. Here, we present recent updates to PED and describe its evolution into a comprehensive resource for extracting, analysing and integrating publicly available multi-omics datasets. A new analytical module has been implemented to run in parallel with the existing literature mining functions. This analytical module has been created using rich data content derived from pancreas-related specimens available through the major data repositories (GEO, ArrayExpress) and international initiatives (TCGA, GENIE, CCLE). Researchers have access to a host of functions to tailor analyses to meet their needs. Results are presented using interactive graphics that allow the molecular data to be visualized in a user-friendly manner. Furthermore, researchers are provided with the means to superimpose layers of molecular information to gain greater insight into alterations and the relationships between them. The literature-mining module has been improved with a redesigned web appearance, restructured query platforms and updated annotations. These updates to PED are in preparation for its integration with the Pancreatic Cancer Research Fund Tissue Bank (PCRFTB), a vital resource of pancreas cancer tissue for researchers to support and promote cutting-edge research.


Subject(s)
Databases, Genetic , Gene Expression , Pancreas/metabolism , Pancreatic Neoplasms/genetics , Animals , DNA Copy Number Variations , Humans , Mice , Mutation , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality
17.
Nucleic Acids Res ; 43(Database issue): D831-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25332396

ABSTRACT

BCCTBbp (http://bioinformatics.breastcancertissue bank.org) was initially developed as the data-mining portal of the Breast Cancer Campaign Tissue Bank (BCCTB), a vital resource of breast cancer tissue for researchers to support and promote cutting-edge research. BCCTBbp is dedicated to maximising research on patient tissues by initially storing genomics, methylomics, transcriptomics, proteomics and microRNA data that has been mined from the literature and linking to pathways and mechanisms involved in breast cancer. Currently, the portal holds 146 datasets comprising over 227,795 expression/genomic measurements from various breast tissues (e.g. normal, malignant or benign lesions), cell lines and body fluids. BCCTBbp can be used to build on breast cancer knowledge and maximise the value of existing research. By recording a large number of annotations on samples and studies, and linking to other databases, such as NCBI, Ensembl and Reactome, a wide variety of different investigations can be carried out. Additionally, BCCTBbp has a dedicated analytical layer allowing researchers to further analyse stored datasets. A future important role for BCCTBbp is to make available all data generated on BCCTB tissues thus building a valuable resource of information on the tissues in BCCTB that will save repetition of experiments and expand scientific knowledge.


Subject(s)
Breast Neoplasms/genetics , Databases, Genetic , Tissue Banks , Breast Neoplasms/metabolism , Computational Biology , Female , Gene Expression Profiling , Genomics , Humans , Internet , Methylation , MicroRNAs/metabolism , Proteomics
18.
Nucleic Acids Res ; 42(Database issue): D944-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24163255

ABSTRACT

The Pancreatic Expression Database (PED, http://www.pancreasexpression.org) is the only device currently available for mining of pancreatic cancer literature data. It brings together the largest collection of multidimensional pancreatic data from the literature including genomic, proteomic, microRNA, methylomic and transcriptomic profiles. PED allows the user to ask specific questions on the observed levels of deregulation among a broad range of specimen/experimental types including healthy/patient tissue and body fluid specimens, cell lines and murine models as well as related treatments/drugs data. Here we provide an update to PED, which has been previously featured in the Database issue of this journal. Briefly, PED data content has been substantially increased and expanded to cover methylomics studies. We introduced an extensive controlled vocabulary that records specific details on the samples and added data from large-scale meta-analysis studies. The web interface has been improved/redesigned with a quick search option to rapidly extract information about a gene/protein of interest and an upload option allowing users to add their own data to PED. We added a user guide and implemented integrated graphical tools to overlay and visualize retrieved information. Interoperability with biomart-compatible data sets was significantly improved to allow integrative queries with pancreatic cancer data.


Subject(s)
Databases, Genetic , Gene Expression , Pancreas/metabolism , Pancreatic Neoplasms/genetics , Animals , Humans , Internet , Mice , Pancreatic Neoplasms/metabolism
19.
J Nanosci Nanotechnol ; 13(12): 8315-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24266229

ABSTRACT

WO3 nanorod based thin films were deposited via pulsed laser deposition onto quartz conductometric transducers with pre-patterned gold interdigitated transducers (IDT) employing the shortest wavelength (193 nm) ArF excimer laser. Micro-characterization techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) were employed to study surface morphology and crystal structure. It was observed that the fabricated films showed nanocolumnar features perpendicular to the surface. The measured sizes of the nanorods were found to be approximately -50 nm in diameter. The high resolution TEM (HRTEM) image of the nanorods based WO3 showed the WO3 lattice spacing of 3.79 angstroms corresponding to the (020) plane of monoclinic WO3. Gas sensing characterizations of the developed sensors were tested towards hydrogen and ethanol at temperatures between room and 400 degrees C. The sensor exhibited high response towards H2 and ethanol at operating temperatures of 170 and 400 degrees C, respectively. The excellent sensing characteristics of WO3 films towards ethanol and H2 at low concentrations offer great potential for low cost and stable gas sensing.

20.
Brief Bioinform ; 14(4): 437-47, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23395730

ABSTRACT

Broader functional annotation of known as well as putative genetic variations is a valuable mean for prioritizing targets in disease studies and large-scale genotyping projects. In this article, we present a practical guide to SNPnexus, a web-based tool that provides an aggregate set of functional annotations for genomic variation data by characterizing related consequences at the transcriptome/proteome levels with in-depth analysis of potential deleterious effects, inferring physical and cytogenetic mapping, reporting related HapMap data, finding overlaps with potential regulatory, structural as well as conserved elements and retrieving links with previously reported genetic disease studies. We focus on the SNPnexus query system, its annotation categories and the biological interpretation of results.


Subject(s)
Genetic Variation , Genomics/methods , Molecular Sequence Annotation , Software , Databases, Genetic , HapMap Project , Polymorphism, Single Nucleotide
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