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  1. Article ; Online: Automated calibration of consensus weighted distance-based clustering approaches using sharp.

    Bodinier, Barbara / Vuckovic, Dragana / Rodrigues, Sabrina / Filippi, Sarah / Chiquet, Julien / Chadeau-Hyam, Marc

    Bioinformatics (Oxford, England)

    2023  Volume 39, Issue 11

    Abstract: Motivation: In consensus clustering, a clustering algorithm is used in combination with a subsampling procedure to detect stable clusters. Previous studies on both simulated and real data suggest that consensus clustering outperforms native algorithms.!# ...

    Abstract Motivation: In consensus clustering, a clustering algorithm is used in combination with a subsampling procedure to detect stable clusters. Previous studies on both simulated and real data suggest that consensus clustering outperforms native algorithms.
    Results: We extend here consensus clustering to allow for attribute weighting in the calculation of pairwise distances using existing regularized approaches. We propose a procedure for the calibration of the number of clusters (and regularization parameter) by maximizing the sharp score, a novel stability score calculated directly from consensus clustering outputs, making it extremely computationally competitive. Our simulation study shows better clustering performances of (i) approaches calibrated by maximizing the sharp score compared to existing calibration scores and (ii) weighted compared to unweighted approaches in the presence of features that do not contribute to cluster definition. Application on real gene expression data measured in lung tissue reveals clear clusters corresponding to different lung cancer subtypes.
    Availability and implementation: The R package sharp (version ≥1.4.3) is available on CRAN at https://CRAN.R-project.org/package=sharp.
    MeSH term(s) Consensus ; Calibration ; Algorithms ; Computer Simulation ; Cluster Analysis
    Language English
    Publishing date 2023-10-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btad635
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  2. Article: Automated calibration for stability selection in penalised regression and graphical models.

    Bodinier, Barbara / Filippi, Sarah / Nøst, Therese Haugdahl / Chiquet, Julien / Chadeau-Hyam, Marc

    Journal of the Royal Statistical Society. Series C, Applied statistics

    2023  Volume 72, Issue 5, Page(s) 1375–1393

    Abstract: Stability selection represents an attractive approach to identify sparse sets of features jointly associated with an outcome in high-dimensional contexts. We introduce an automated calibration procedure via maximisation of an in-house stability score and ...

    Abstract Stability selection represents an attractive approach to identify sparse sets of features jointly associated with an outcome in high-dimensional contexts. We introduce an automated calibration procedure via maximisation of an in-house stability score and accommodating a priori-known block structure (e.g. multi-OMIC) data. It applies to [Least Absolute Shrinkage Selection Operator (LASSO)] penalised regression and graphical models. Simulations show our approach outperforms non-stability-based and stability selection approaches using the original calibration. Application to multi-block graphical LASSO on real (epigenetic and transcriptomic) data from the Norwegian Women and Cancer study reveals a central/credible and novel cross-OMIC role of LRRN3 in the biological response to smoking. Proposed approaches were implemented in the R package sharp.
    Language English
    Publishing date 2023-07-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 1482300-7
    ISSN 1467-9876 ; 0035-9254
    ISSN (online) 1467-9876
    ISSN 0035-9254
    DOI 10.1093/jrsssc/qlad058
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  3. Article ; Online: Association Between Purchase of Over-the-Counter Medications and Ovarian Cancer Diagnosis in the Cancer Loyalty Card Study (CLOCS): Observational Case-Control Study.

    Brewer, Hannah R / Hirst, Yasemin / Chadeau-Hyam, Marc / Johnson, Eric / Sundar, Sudha / Flanagan, James M

    JMIR public health and surveillance

    2023  Volume 9, Page(s) e41762

    Abstract: Background: Over-the-counter (OTC) medications are frequently used to self-care for nonspecific ovarian cancer symptoms prior to diagnosis. Monitoring such purchases may provide an opportunity for earlier diagnosis.: Objective: The aim of the Cancer ... ...

    Abstract Background: Over-the-counter (OTC) medications are frequently used to self-care for nonspecific ovarian cancer symptoms prior to diagnosis. Monitoring such purchases may provide an opportunity for earlier diagnosis.
    Objective: The aim of the Cancer Loyalty Card Study (CLOCS) was to investigate purchases of OTC pain and indigestion medications prior to ovarian cancer diagnosis in women with and without ovarian cancer in the United Kingdom using loyalty card data.
    Methods: An observational case-control study was performed comparing purchases of OTC pain and indigestion medications prior to diagnosis in women with (n=153) and without (n=120) ovarian cancer using loyalty card data from two UK-based high street retailers. Monthly purchases of pain and indigestion medications for cases and controls were compared using the Fisher exact test, conditional logistic regression, and receiver operating characteristic (ROC) curve analysis.
    Results: Pain and indigestion medication purchases were increased among cases 8 months before diagnosis, with maximum discrimination between cases and controls 8 months before diagnosis (Fisher exact odds ratio [OR] 2.9, 95% CI 2.1-4.1). An increase in indigestion medication purchases was detected up to 9 months before diagnosis (adjusted conditional logistic regression OR 1.38, 95% CI 1.04-1.83). The ROC analysis for indigestion medication purchases showed a maximum area under the curve (AUC) at 13 months before diagnosis (AUC=0.65, 95% CI 0.57-0.73), which further improved when stratified to late-stage ovarian cancer (AUC=0.68, 95% CI 0.59-0.78).
    Conclusions: There is a difference in purchases of pain and indigestion medications among women with and without ovarian cancer up to 8 months before diagnosis. Facilitating earlier presentation among those who self-care for symptoms using this novel data source could improve ovarian cancer patients' options for treatment and improve survival.
    Trial registration: ClinicalTrials.gov NCT03994653; https://clinicaltrials.gov/ct2/show/NCT03994653.
    MeSH term(s) Humans ; Female ; Case-Control Studies ; Dyspepsia ; Early Detection of Cancer ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Pain
    Language English
    Publishing date 2023-01-26
    Publishing country Canada
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2369-2960
    ISSN (online) 2369-2960
    DOI 10.2196/41762
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  4. Article ; Online: Cancer Loyalty Card Study (CLOCS): feasibility outcomes for an observational case-control study focusing on the patient interval in ovarian cancer.

    Brewer, Hannah R / Chadeau-Hyam, Marc / Johnson, Eric / Sundar, Sudha / Flanagan, James / Hirst, Yasemin

    BMJ open

    2023  Volume 13, Issue 6, Page(s) e066022

    Abstract: Objectives: Ovarian cancer symptoms are often non-specific and can be normalised before patients seek medical help. The Cancer Loyalty Card Study investigated self-management behaviours of patients with ovarian cancer prior to their diagnosis using ... ...

    Abstract Objectives: Ovarian cancer symptoms are often non-specific and can be normalised before patients seek medical help. The Cancer Loyalty Card Study investigated self-management behaviours of patients with ovarian cancer prior to their diagnosis using loyalty card data collected by two UK-based high street retailers. Here, we discuss the feasibility outcomes for this novel research.
    Design: Observational case-control study.
    Setting: Control participants were invited to the study using social media and other sources from the general public. Once consented, control participants were required to submit proof of identification (ID) for their loyalty card data to be shared. Cases were identified using unique National Health Service (NHS) numbers (a proxy for ID) and were recruited through 12 NHS tertiary care clinics.
    Participants: Women in the UK, 18 years or older, with at least one of the participating high street retailers' loyalty cards. Those with an ovarian cancer diagnosis within 2 years of recruitment were considered cases, and those without an ovarian cancer diagnosis were considered controls.
    Primary outcome measures: Recruitment rates, demographics of participants and identification of any barriers to recruitment.
    Results: In total, 182 cases and 427 controls were recruited with significant differences by age, number of people in participants' households and the geographical region in the UK. However, only 37% (n=160/427) of control participants provided sufficient ID details and 81% (n=130/160) matched retailers' records. The majority of the participants provided complete responses to the 24-Item Ovarian Risk Questionnaire.
    Conclusions: Our findings show that recruitment to a study aiming to understand self-care behaviours using loyalty card data is challenging but feasible. The general public were willing to share their data for health research. Barriers in data sharing mechanisms need to be addressed to maximise participant retention.
    Trial registration number: ISRCTN14897082, CPMS 43323, NCT03994653.
    MeSH term(s) Humans ; Female ; Case-Control Studies ; Feasibility Studies ; State Medicine ; Ovarian Neoplasms/therapy ; Publications
    Language English
    Publishing date 2023-06-14
    Publishing country England
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2022-066022
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  5. Article ; Online: Strategic use of SARS-CoV-2 wastewater concentration data could enhance, but not replace, high-resolution community prevalence survey programmes

    Mills, Cathal / Chadeau-Hyam, Marc / Elliott, Paul L / Donnelly, Christl A

    medRxiv

    Abstract: Wastewater-based epidemiology (WBE) has been proposed as a tool for public health authorities to monitor community transmission of SARS-CoV-2 and other agents. Here, we review the utility of WBE for estimating SARS-CoV-2 prevalence using wastewater data ... ...

    Abstract Wastewater-based epidemiology (WBE) has been proposed as a tool for public health authorities to monitor community transmission of SARS-CoV-2 and other agents. Here, we review the utility of WBE for estimating SARS-CoV-2 prevalence using wastewater data from the Environmental Monitoring for Health Protection (EMHP) programme and prevalence data from the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. Our analysis shows a temporally evolving relationship between wastewater and prevalence which limits the utility of WBE for estimating SARS-CoV-2 prevalence in high spatial resolution without a concurrent prevalence survey. We further characterise WBE for SARS-CoV-2 prevalence as i) vaccination-coverage-dependent and ii) variant-specific. Our work provides a gesopatial framework to map wastewater concentrations to public health boundaries, enabling public health authorities to interpret the relationship between wastewater and prevalence. We demonstrate that WBE can improve the cost efficiency and accuracy of community prevalence surveys which on their own may have incomplete geographic coverage or small sample sizes.
    Keywords covid19
    Language English
    Publishing date 2023-08-20
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.08.17.23293589
    Database COVID19

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  6. Article ; Online: Biological age estimation using circulating blood biomarkers.

    Bortz, Jordan / Guariglia, Andrea / Klaric, Lucija / Tang, David / Ward, Peter / Geer, Michael / Chadeau-Hyam, Marc / Vuckovic, Dragana / Joshi, Peter K

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 1089

    Abstract: Biological age captures physiological deterioration better than chronological age and is amenable to interventions. Blood-based biomarkers have been identified as suitable candidates for biological age estimation. This study aims to improve biological ... ...

    Abstract Biological age captures physiological deterioration better than chronological age and is amenable to interventions. Blood-based biomarkers have been identified as suitable candidates for biological age estimation. This study aims to improve biological age estimation using machine learning models and a feature-set of 60 circulating biomarkers available from the UK Biobank (n = 306,116). We implement an Elastic-Net derived Cox model with 25 selected biomarkers to predict mortality risk (C-Index = 0.778; 95% CI [0.767-0.788]), which outperforms the well-known blood-biomarker based PhenoAge model (C-Index = 0.750; 95% CI [0.739-0.761]), providing a C-Index lift of 0.028 representing an 11% relative increase in predictive value. Importantly, we then show that using common clinical assay panels, with few biomarkers, alongside imputation and the model derived on the full set of biomarkers, does not substantially degrade predictive accuracy from the theoretical maximum achievable for the available biomarkers. Biological age is estimated as the equivalent age within the same-sex population which corresponds to an individual's mortality risk. Values ranged between 20-years younger and 20-years older than individuals' chronological age, exposing the magnitude of ageing signals contained in blood markers. Thus, we demonstrate a practical and cost-efficient method of estimating an improved measure of Biological Age, available to the general population.
    MeSH term(s) Humans ; Aging/physiology ; Biomarkers
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-10-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05456-z
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  7. Article ; Online: Cancer Loyalty Card Study (CLOCS)

    Marc Chadeau-Hyam / Sudha Sundar / Yasemin Hirst / Hannah R Brewer / James Flanagan / Eric Johnson

    BMJ Open, Vol 13, Iss

    feasibility outcomes for an observational case–control study focusing on the patient interval in ovarian cancer

    2023  Volume 6

    Abstract: Objectives Ovarian cancer symptoms are often non-specific and can be normalised before patients seek medical help. The Cancer Loyalty Card Study investigated self-management behaviours of patients with ovarian cancer prior to their diagnosis using ... ...

    Abstract Objectives Ovarian cancer symptoms are often non-specific and can be normalised before patients seek medical help. The Cancer Loyalty Card Study investigated self-management behaviours of patients with ovarian cancer prior to their diagnosis using loyalty card data collected by two UK-based high street retailers. Here, we discuss the feasibility outcomes for this novel research.Design Observational case–control study.Setting Control participants were invited to the study using social media and other sources from the general public. Once consented, control participants were required to submit proof of identification (ID) for their loyalty card data to be shared. Cases were identified using unique National Health Service (NHS) numbers (a proxy for ID) and were recruited through 12 NHS tertiary care clinics.Participants Women in the UK, 18 years or older, with at least one of the participating high street retailers’ loyalty cards. Those with an ovarian cancer diagnosis within 2 years of recruitment were considered cases, and those without an ovarian cancer diagnosis were considered controls.Primary outcome measures Recruitment rates, demographics of participants and identification of any barriers to recruitment.Results In total, 182 cases and 427 controls were recruited with significant differences by age, number of people in participants’ households and the geographical region in the UK. However, only 37% (n=160/427) of control participants provided sufficient ID details and 81% (n=130/160) matched retailers’ records. The majority of the participants provided complete responses to the 24-Item Ovarian Risk Questionnaire.Conclusions Our findings show that recruitment to a study aiming to understand self-care behaviours using loyalty card data is challenging but feasible. The general public were willing to share their data for health research. Barriers in data sharing mechanisms need to be addressed to maximise participant retention.Trial registration number ISRCTN14897082, CPMS 43323, NCT03994653.
    Keywords Medicine ; R
    Subject code 150
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Hair-Derived Exposome Exploration of Cardiometabolic Health: Piloting a Bayesian Multitrait Variable Selection Approach.

    Wada, Rin / Peng, Feng-Jiao / Lin, Chia-An / Vermeulen, Roel / Iglesias-González, Alba / Palazzi, Paul / Bodinier, Barbara / Streel, Sylvie / Guillaume, Michèle / Vuckovic, Dragana / Dagnino, Sonia / Chiquet, Julien / Appenzeller, Brice M R / Chadeau-Hyam, Marc

    Environmental science & technology

    2024  Volume 58, Issue 12, Page(s) 5383–5393

    Abstract: Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in- ...

    Abstract Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (
    MeSH term(s) Humans ; Exposome ; Bayes Theorem ; Obesity/epidemiology ; Hypertension ; Hair ; Dyslipidemias ; Environmental Exposure
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ISSN 1520-5851
    ISSN (online) 1520-5851
    DOI 10.1021/acs.est.3c08739
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  9. Article ; Online: A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer.

    Vermeulen, Roel / Bodinier, Barbara / Dagnino, Sonia / Wada, Rin / Wang, Xuting / Silverman, Debra / Albanes, Demetrius / Freedman, Neal / Rahman, Mohammad / Bell, Douglas / Chadeau-Hyam, Marc / Rothman, Nathaniel

    European journal of epidemiology

    2024  

    Abstract: Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We ... ...

    Abstract Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case-control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine-phosphate-guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59-0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63-0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation.
    Language English
    Publishing date 2024-03-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 632614-6
    ISSN 1573-7284 ; 0393-2990
    ISSN (online) 1573-7284
    ISSN 0393-2990
    DOI 10.1007/s10654-024-01110-y
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  10. Article ; Online: Cognition and Memory after Covid-19 in a Large Community Sample.

    Hampshire, Adam / Azor, Adriana / Atchison, Christina / Trender, William / Hellyer, Peter J / Giunchiglia, Valentina / Husain, Masud / Cooke, Graham S / Cooper, Emily / Lound, Adam / Donnelly, Christl A / Chadeau-Hyam, Marc / Ward, Helen / Elliott, Paul

    The New England journal of medicine

    2024  Volume 390, Issue 9, Page(s) 806–818

    Abstract: Background: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they ... ...

    Abstract Background: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.
    Methods: We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating ("brain fog").
    Results: Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.
    Conclusions: Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).
    MeSH term(s) Adult ; Humans ; Cognition ; Cognitive Dysfunction/etiology ; COVID-19/complications ; Memory Disorders/etiology ; SARS-CoV-2 ; Memory ; England ; Post-Acute COVID-19 Syndrome/etiology
    Language English
    Publishing date 2024-02-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMoa2311330
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