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  1. Article ; Online: Place of concordance-discordance model in evaluating NGS performance.

    Zhai, Yue / Bardel, Claire / Vallée, Maxime / Iwaz, Jean / Roy, Pascal

    Human heredity

    2024  

    Abstract: Introduction: Ideally, evaluating NGS performance requires a gold standard; in its absence, concordance between replicates is often used as substitute standard. However, the appropriateness of the concordance-discordance criterion has been rarely ... ...

    Abstract Introduction: Ideally, evaluating NGS performance requires a gold standard; in its absence, concordance between replicates is often used as substitute standard. However, the appropriateness of the concordance-discordance criterion has been rarely evaluated. This study analyzes the relationship between the probability of discordance and the probability of error under different conditions.
    Methods: This study used a conditional probability approach under conditional dependence then conditional independence between two sequencing results and compares the probabilities of discordance and error in different theoretical conditions of sensitivity, specificity, and correlation between replicates, then on real results of sequencing genome NA12878. The study examines also covariate effects on discordance and error using generalized additive models with smooth functions.
    Results: With 99% sensitivity and 99.9% specificity under conditional independence, the probability of error for a positive concordant pair of calls is 0.1%. With additional hypotheses of 0.1% prevalence and 0.9 correlation between replicates, the probability of error for a positive concordant pair is 47.4%. With real data, the estimated sensitivity, specificity, and correlation between tests for variants are around 98.98%, 99.996%, and 93%, respectively, and the error rate for positive concordant calls approximates 2.5%. In covariate effect analyses, the effects' functional form are close between discordance and error models, though the parts of deviance explained by the covariates differ between discordance and error models.
    Conclusion: With conditional independence of two sequencing results, the concordance-discordance criterion seems acceptable as substitute standard. However, with high correlation, the criterion becomes questionable because a high percentage of false concordant results appears among concordant results.
    Language English
    Publishing date 2024-03-16
    Publishing country Switzerland
    Document type News
    ZDB-ID 2424-7
    ISSN 1423-0062 ; 0001-5652
    ISSN (online) 1423-0062
    ISSN 0001-5652
    DOI 10.1159/000538401
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  2. Article: Performance comparisons between clustering models for reconstructing NGS results from technical replicates.

    Zhai, Yue / Bardel, Claire / Vallée, Maxime / Iwaz, Jean / Roy, Pascal

    Frontiers in genetics

    2023  Volume 14, Page(s) 1148147

    Abstract: To improve the performance of individual DNA sequencing results, researchers often use replicates from the same individual and various statistical clustering models to reconstruct a high-performance callset. Here, three technical replicates of genome ... ...

    Abstract To improve the performance of individual DNA sequencing results, researchers often use replicates from the same individual and various statistical clustering models to reconstruct a high-performance callset. Here, three technical replicates of genome NA12878 were considered and five model types were compared (consensus, latent class, Gaussian mixture, Kamila-adapted k-means, and random forest) regarding four performance indicators: sensitivity, precision, accuracy, and F1-score. In comparison with no use of a combination model, i) the consensus model improved precision by 0.1%; ii) the latent class model brought 1% precision improvement (97%-98%) without compromising sensitivity (= 98.9%); iii) the Gaussian mixture model and random forest provided callsets with higher precisions (both >99%) but lower sensitivities; iv) Kamila increased precision (>99%) and kept a high sensitivity (98.8%); it showed the best overall performance. According to precision and F1-score indicators, the compared non-supervised clustering models that combine multiple callsets are able to improve sequencing performance vs. previously used supervised models. Among the models compared, the Gaussian mixture model and Kamila offered non-negligible precision and F1-score improvements. These models may be thus recommended for callset reconstruction (from either biological or technical replicates) for diagnostic or precision medicine purposes.
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2023.1148147
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  3. Article ; Online: Renal and major clinical outcomes and their determinants after nephrectomy in patients with pre-existing chronic kidney disease: A retrospective cohort study.

    Schleef, Maxime / Roy, Pascal / Lemoine, Sandrine / Paparel, Philippe / Colombel, Marc / Badet, Lionel / Guebre-Egziabher, Fitsum

    PloS one

    2024  Volume 19, Issue 5, Page(s) e0300367

    Abstract: The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or ...

    Abstract The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.
    MeSH term(s) Humans ; Nephrectomy/adverse effects ; Nephrectomy/methods ; Male ; Female ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/surgery ; Renal Insufficiency, Chronic/physiopathology ; Retrospective Studies ; Middle Aged ; Aged ; Glomerular Filtration Rate ; Risk Factors ; Kidney Neoplasms/surgery ; Kidney Neoplasms/complications ; Postoperative Complications/etiology ; Postoperative Complications/epidemiology ; Treatment Outcome ; Kidney/surgery ; Kidney/physiopathology ; Solitary Kidney/surgery ; Solitary Kidney/complications
    Language English
    Publishing date 2024-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0300367
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  4. Article ; Online: Artificial Intelligence as a Decision-Making Tool in Forensic Dentistry: A Pilot Study with I3M.

    Bui, Romain / Iozzino, Régis / Richert, Raphaël / Roy, Pascal / Boussel, Loïc / Tafrount, Cheraz / Ducret, Maxime

    International journal of environmental research and public health

    2023  Volume 20, Issue 5

    Abstract: Expert determination of the third molar maturity index (I3M) constitutes one of the most common approaches for dental age estimation. This work aimed to investigate the technical feasibility of creating a decision-making tool based on I3M to support ... ...

    Abstract Expert determination of the third molar maturity index (I3M) constitutes one of the most common approaches for dental age estimation. This work aimed to investigate the technical feasibility of creating a decision-making tool based on I3M to support expert decision-making. Methods: The dataset consisted of 456 images from France and Uganda. Two deep learning approaches (Mask R-CNN, U-Net) were compared on mandibular radiographs, leading to a two-part instance segmentation (apical and coronal). Then, two topological data analysis approaches were compared on the inferred mask: one with a deep learning component (TDA-DL), one without (TDA). Regarding mask inference, U-Net had a better accuracy (mean intersection over union metric (mIoU)), 91.2% compared to 83.8% for Mask R-CNN. The combination of U-Net with TDA or TDA-DL to compute the I3M score revealed satisfying results in comparison with a dental forensic expert. The mean ± SD absolute error was 0.04 ± 0.03 for TDA, and 0.06 ± 0.04 for TDA-DL. The Pearson correlation coefficient of the I3M scores between the expert and a U-Net model was 0.93 when combined with TDA and 0.89 with TDA-DL. This pilot study illustrates the potential feasibility to automate an I3M solution combining a deep learning and a topological approach, with 95% accuracy in comparison with an expert.
    MeSH term(s) Artificial Intelligence ; Pilot Projects ; Forensic Dentistry ; Age Determination by Teeth/methods
    Language English
    Publishing date 2023-03-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph20054620
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  5. Article ; Online: Integrating imaging-based classification and transcriptomics for quality assessment of human oocytes according to their reproductive efficiency.

    Viñals Gonzalez, Xavier / Thrasivoulou, Christopher / Naja, Roy Pascal / Seshadri, Srividya / Serhal, Paul / Gupta, Sioban Sen

    Journal of assisted reproduction and genetics

    2023  Volume 40, Issue 11, Page(s) 2545–2556

    Abstract: Purpose: Utilising non-invasive imaging parameters to assess human oocyte fertilisation, development and implantation; and their influence on transcriptomic profiles.: Methods: A ranking tool was designed using imaging data from 957 metaphase II ... ...

    Abstract Purpose: Utilising non-invasive imaging parameters to assess human oocyte fertilisation, development and implantation; and their influence on transcriptomic profiles.
    Methods: A ranking tool was designed using imaging data from 957 metaphase II stage oocytes retrieved from 102 patients undergoing ART. Hoffman modulation contrast microscopy was conducted with an Olympus IX53 microscope. Images were acquired prior to ICSI and processed using ImageJ for optical density and grey-level co-occurrence matrices texture analysis. Single-cell RNA sequencing of twenty-three mature oocytes classified according to their competence was performed.
    Result(s): Overall fertilisation, blastulation and implantation rates were 73.0%, 62.6% and 50.8%, respectively. Three different algorithms were produced using binary logistic regression methods based on "optimal" quartiles, resulting in an accuracy of prediction of 76.6%, 67% and 80.7% for fertilisation, blastulation and implantation. Optical density, gradient, inverse difference moment (homogeneity) and entropy (structural complexity) were the parameters with highest predictive properties. The ranking tool showed high sensitivity (68.9-90.8%) but with limited specificity (26.5-62.5%) for outcome prediction. Furthermore, five differentially expressed genes were identified when comparing "good" versus "poor" competent oocytes.
    Conclusion(s): Imaging properties can be used as a tool to assess differences in the ooplasm and predict laboratory and clinical outcomes. Transcriptomic analysis suggested that oocytes with lower competence may have compromised cell cycle either by non-reparable DNA damage or insufficient ooplasmic maturation. Further development of algorithms based on image parameters is encouraged, with an increased balanced cohort and validated prospectively in multicentric studies.
    MeSH term(s) Humans ; Transcriptome/genetics ; Oocytes ; Oogenesis/genetics ; Embryo Implantation ; Gene Expression Profiling
    Language English
    Publishing date 2023-08-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1112577-9
    ISSN 1573-7330 ; 1058-0468
    ISSN (online) 1573-7330
    ISSN 1058-0468
    DOI 10.1007/s10815-023-02911-y
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  6. Article ; Online: FlauBERT vs. CamemBERT: Understanding patient's answers by a French medical chatbot.

    Blanc, Corentin / Bailly, Alexandre / Francis, Élie / Guillotin, Thierry / Jamal, Fadi / Wakim, Béchara / Roy, Pascal

    Artificial intelligence in medicine

    2022  Volume 127, Page(s) 102264

    Abstract: In a number of circumstances, obtaining health-related information from a patient is time-consuming, whereas a chatbot interacting efficiently with that patient might help saving health care professional time and better assisting the patient. Making a ... ...

    Abstract In a number of circumstances, obtaining health-related information from a patient is time-consuming, whereas a chatbot interacting efficiently with that patient might help saving health care professional time and better assisting the patient. Making a chatbot understand patients' answers uses Natural Language Understanding (NLU) technology that relies on 'intent' and 'slot' predictions. Over the last few years, language models (such as BERT) pre-trained on huge amounts of data achieved state-of-the-art intent and slot predictions by connecting a neural network architecture (e.g., linear, recurrent, long short-term memory, or bidirectional long short-term memory) and fine-tuning all language model and neural network parameters end-to-end. Currently, two language models are specialized in French language: FlauBERT and CamemBERT. This study was designed to find out which combination of language model and neural network architecture was the best for intent and slot prediction by a chatbot from a French corpus of clinical cases. The comparisons showed that FlauBERT performed better than CamemBERT whatever the network architecture used and that complex architectures did not significantly improve performance vs. simple ones whatever the language model. Thus, in the medical field, the results support recommending FlauBERT with a simple linear network architecture.
    MeSH term(s) Humans ; Intention ; Language ; Natural Language Processing ; Neural Networks, Computer ; Software
    Language English
    Publishing date 2022-03-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645179-2
    ISSN 1873-2860 ; 0933-3657
    ISSN (online) 1873-2860
    ISSN 0933-3657
    DOI 10.1016/j.artmed.2022.102264
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    Zs.A 2547: Show issues Location:
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  7. Article ; Online: Individualized Net Benefit estimation and meta-analysis using generalized pairwise comparisons in N-of-1 trials.

    Giai, Joris / Péron, Julien / Roustit, Matthieu / Cracowski, Jean-Luc / Roy, Pascal / Ozenne, Brice / Buyse, Marc / Maucort-Boulch, Delphine

    Statistics in medicine

    2023  

    Abstract: Background: The Net Benefit (Δ) is a measure of the benefit-risk balance in clinical trials, based on generalized pairwise comparisons (GPC) using several prioritized outcomes and thresholds of clinical relevance. We extended Δ to N-of-1 trials, with a ... ...

    Abstract Background: The Net Benefit (Δ) is a measure of the benefit-risk balance in clinical trials, based on generalized pairwise comparisons (GPC) using several prioritized outcomes and thresholds of clinical relevance. We extended Δ to N-of-1 trials, with a focus on patient-level and population-level Δ.
    Methods: We developed a Δ estimator at the individual level as an extension of the stratum-specific Δ, and at the population-level as an extension of the stratified Δ. We performed a simulation study mimicking PROFIL, a series of 38 N-of-1 trials testing sildenafil in Raynaud's phenomenon, to assess the power for such an analysis with realistic data. We then reanalyzed PROFIL using GPC. This reanalysis was finally interpreted in the context of the main analysis of PROFIL which used Bayesian individual probabilities of efficacy.
    Results: Simulations under the null showed good size of the test for both individual and population levels. The test lacked power when being simulated from the true PROFIL data, even when increasing the number of repetitions up to 140 days per patient. PROFIL individual-level estimated Δ were well correlated with the probabilities of efficacy from the Bayesian analysis while showing similarly wide confidence intervals. Population-level estimated Δ was not significantly different from zero, consistently with the previous Bayesian analysis.
    Conclusion: GPC can be used to estimate individual Δ which can then be aggregated in a meta-analytic way in N-of-1 trials. GPC ability to easily incorporate patient preferences allow for more personalized treatment evaluation, while needing much less computing time than Bayesian modeling.
    Language English
    Publishing date 2023-01-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 843037-8
    ISSN 1097-0258 ; 0277-6715
    ISSN (online) 1097-0258
    ISSN 0277-6715
    DOI 10.1002/sim.9648
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    Zs.A 1756: Show issues Location:
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  8. Article ; Online: Optimism Bias Correction in Omics Studies with Big Data: Assessment of Penalized Methods on Simulated Data.

    Zhao, Yubing / Dantony, Emmanuelle / Roy, Pascal

    Omics : a journal of integrative biology

    2019  Volume 23, Issue 4, Page(s) 207–213

    Abstract: Big Data generated by omics technologies require simultaneous analyses of large numbers of variables. This leads to complex model selection and parameter estimates that show optimism bias. This study on simulated data sets examined optimism-bias ... ...

    Abstract Big Data generated by omics technologies require simultaneous analyses of large numbers of variables. This leads to complex model selection and parameter estimates that show optimism bias. This study on simulated data sets examined optimism-bias correction by penalty regression methods in case-control studies that involve clinical and omics variables. Least absolute shrinkage and selection operator (LASSO)-based methods (LASSO-penalized logistic regression, adaptive LASSO, and regularized LASSO for selection + ridge regression) were evaluated using power, the false positive rate (FPR), false discovery rate (FDR), and by estimated versus theoretical parameter comparisons. The "ordinary" LASSO overcorrects the optimism bias. The adaptive LASSO with LASSO estimation of the weights was unable to provide a sufficient correction. Importantly, the adaptive LASSO with ridge estimation of the weights showed the best parameter estimation. The regularized LASSO selection showed a slight optimism bias that decreased with the increase in the training set size. The optimism bias decreased with the increase of the number of variables selected among truly differentially expressed variables; however, power, FPR, and FDR were correlated. A compromise between model selection and estimation accuracy should be found. These results might prove useful because Big Data analyses are becoming commonplace in omics/multiomics studies in integrative biology, precision medicine, and planetary health.
    MeSH term(s) Case-Control Studies ; Databases, Factual ; Humans ; Logistic Models ; Precision Medicine ; Regression Analysis
    Language English
    Publishing date 2019-02-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2030312-9
    ISSN 1557-8100 ; 1536-2310
    ISSN (online) 1557-8100
    ISSN 1536-2310
    DOI 10.1089/omi.2018.0191
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  9. Article ; Online: Multiple xenoestrogen air pollutants and breast cancer risk: Statistical approaches to investigate combined exposures effect.

    Amadou, Amina / Giampiccolo, Camille / Bibi Ngaleu, Fabiola / Praud, Delphine / Coudon, Thomas / Grassot, Lény / Faure, Elodie / Couvidat, Florian / Frenoy, Pauline / Severi, Gianluca / Romana Mancini, Francesca / Roy, Pascal / Fervers, Béatrice

    Environmental pollution (Barking, Essex : 1987)

    2024  Volume 351, Page(s) 124043

    Abstract: Studies suggested that exposure to air pollutants, with endocrine disrupting (ED) properties, have a key role in breast cancer (BC) development. Although the population is exposed simultaneously to a mixture of multiple pollutants and ED pollutants may ... ...

    Abstract Studies suggested that exposure to air pollutants, with endocrine disrupting (ED) properties, have a key role in breast cancer (BC) development. Although the population is exposed simultaneously to a mixture of multiple pollutants and ED pollutants may act via common biological mechanisms leading to synergic effects, epidemiological studies generally evaluate the effect of each pollutant separately. We aimed to assess the complex effect of exposure to a mixture of four xenoestrogen air pollutants (benzo-[a]-pyrene (BaP), cadmium, dioxin (2,3,7,8-Tétrachlorodibenzo-p-dioxin TCDD)), and polychlorinated biphenyl 153 (PCB153)) on the risk of BC, using three recent statistical methods, namely weighted quantile sum (WQS), quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR). The study was conducted on 5222 cases and 5222 matched controls nested within the French prospective E3N cohort initiated in 1990. Annual average exposure estimates to the pollutants were assessed using a chemistry transport model, at the participants' residence address between 1990 and 2011. We found a positive association between the WQS index of the joint effect and the risk of overall BC (adjusted odds ratio (OR) = 1.10, 95% confidence intervals (CI): 1.03-1.19). Similar results were found for QGC (OR = 1.11, 95%CI: 1.03-1.19). Despite the association did not reach statistical significance in the BKMR model, we observed an increasing trend between the joint effect of the four pollutants and the risk of BC, when fixing other chemicals at their median concentrations. BaP, cadmium and PCB153 also showed positive trends in the multi-pollutant mixture, while dioxin showed a modest inverse trend. Despite we found a clear evidence of a positive association between the joint exposure to pollutants and BC risk only from WQS and QGC regression, we observed a similar suggestive trend using BKMR. This study makes a major contribution to the understanding of the joint effects of air pollution.
    Language English
    Publishing date 2024-04-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 280652-6
    ISSN 1873-6424 ; 0013-9327 ; 0269-7491
    ISSN (online) 1873-6424
    ISSN 0013-9327 ; 0269-7491
    DOI 10.1016/j.envpol.2024.124043
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  10. Article ; Online: Incidence and risk factors for bilateral proximal femoral fractures.

    Van Haecke, Adrien / Viste, Anthony / Desmarchelier, Romain / Roy, Pascal / Mercier, Marcelle / Fessy, Michel-Henri

    Orthopaedics & traumatology, surgery & research : OTSR

    2021  Volume 108, Issue 1, Page(s) 102887

    Abstract: Background: Proximal femoral fractures (PFFs) are a public health issue due to their high frequency. The frequency of a second PFF on the other side is estimated at 10%. This estimation is controversial, however, and the risk factors have not been ... ...

    Abstract Background: Proximal femoral fractures (PFFs) are a public health issue due to their high frequency. The frequency of a second PFF on the other side is estimated at 10%. This estimation is controversial, however, and the risk factors have not been evaluated in a large population of French patients. The objective of this retrospective case-control study was to determine: (1) the incidence of second PFFs and (2) their risk factors.
    Hypothesis: The incidence of second PFFs is >2% after 1 year and >5% after 3 years.
    Material and methods: We conducted a case-control study in a population of consecutive patients managed surgically for PPF at the Lyon Sud Hospital between 2013 and 2014. We analysed the following clinical factors: age, sex, body mass index (BMI), institutionalisation, the Parker score, the American Society of Anesthesiologists score (ASA), comorbidities, and the use of psychoactive drugs.
    Results: We included 474 PFFs (trochanter, n=240 and neck, n=234) of which 36 were bilateral. The contralateral fracture occurred within 1 year of the first fracture in 6/474 (1.3%) cases and within 3 years in all 36 cases (7.6%). The case-control study comprised 49 cases with bilateral PFF and 161 controls with no second hip fracture within 3 years. Risk factors for a second hip fracture were age older than 90 years (odds ratio [OR]=5.44; 95% confidence interval [95%CI], 112-2642 (p=0.002)) and a history of heart disease (OR, 2.18; 95%CI, 1.06-4.47 [p=0.03]). A Parker score≥6 was protective (OR, 0.84; 95%CI, 0.71-0.99 [p=0.03]). Mortality after 3 years was 42% (201/474), and 13% (63/474) of patients were lost to follow-up.
    Discussion: Age older than 90 years, a Parker score below 6, and a history of heart disease are risk factors for a second PFF within 3 years after the first PFF.
    Level of evidence: III; case-control study.
    MeSH term(s) Aged, 80 and over ; Arthroplasty, Replacement, Hip/adverse effects ; Case-Control Studies ; Femoral Fractures/epidemiology ; Femoral Fractures/etiology ; Femoral Fractures/surgery ; Heart Diseases/complications ; Hip Fractures/complications ; Humans ; Incidence ; Periprosthetic Fractures/surgery ; Retrospective Studies ; Risk Factors
    Language English
    Publishing date 2021-03-09
    Publishing country France
    Document type Journal Article
    ISSN 1877-0568
    ISSN (online) 1877-0568
    DOI 10.1016/j.otsr.2021.102887
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