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Murali Sundaram - One of the best experts on this subject based on the ideXlab platform.
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hiscr hidradenitis suppurativa Clinical response a novel Clinical Endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo controlled portion of a phase 2 adalimumab study
Journal of The European Academy of Dermatology and Venereology, 2016Co-Authors: Alexa B. Kimball, Yihua Gu, Murali Sundaram, Jeffrey M Sobell, Christos C Zouboulis, David A Williams, H D Teixeira, Gregor B. E. JemecAbstract:Background Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Objective Evaluate the novel, validated Endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. Methods Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). Results The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. Conclusion HiSCR was more responsive to change than HS-PGA Response in this subpopulation.
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assessing the validity responsiveness and meaningfulness of the hidradenitis suppurativa Clinical response hiscr as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P < 0·001). Improvements of all PROs in HiSCR achievers exceeded the respective meaningful improvement thresholds. Conclusions In patients with HS with ≥ 3 ANs, HiSCR achievers had significant improvements in physician-rated and patient-reported HS disease severity and impact. HiSCR is a valid and meaningful Endpoint for assessing HS treatment effectiveness in controlling inflammatory manifestations in this population.
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Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P
Gregor B. E. Jemec - One of the best experts on this subject based on the ideXlab platform.
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hiscr hidradenitis suppurativa Clinical response a novel Clinical Endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo controlled portion of a phase 2 adalimumab study
Journal of The European Academy of Dermatology and Venereology, 2016Co-Authors: Alexa B. Kimball, Yihua Gu, Murali Sundaram, Jeffrey M Sobell, Christos C Zouboulis, David A Williams, H D Teixeira, Gregor B. E. JemecAbstract:Background Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Objective Evaluate the novel, validated Endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. Methods Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). Results The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. Conclusion HiSCR was more responsive to change than HS-PGA Response in this subpopulation.
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assessing the validity responsiveness and meaningfulness of the hidradenitis suppurativa Clinical response hiscr as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P < 0·001). Improvements of all PROs in HiSCR achievers exceeded the respective meaningful improvement thresholds. Conclusions In patients with HS with ≥ 3 ANs, HiSCR achievers had significant improvements in physician-rated and patient-reported HS disease severity and impact. HiSCR is a valid and meaningful Endpoint for assessing HS treatment effectiveness in controlling inflammatory manifestations in this population.
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Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P
Alexa B. Kimball - One of the best experts on this subject based on the ideXlab platform.
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hiscr hidradenitis suppurativa Clinical response a novel Clinical Endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo controlled portion of a phase 2 adalimumab study
Journal of The European Academy of Dermatology and Venereology, 2016Co-Authors: Alexa B. Kimball, Yihua Gu, Murali Sundaram, Jeffrey M Sobell, Christos C Zouboulis, David A Williams, H D Teixeira, Gregor B. E. JemecAbstract:Background Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Objective Evaluate the novel, validated Endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. Methods Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). Results The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. Conclusion HiSCR was more responsive to change than HS-PGA Response in this subpopulation.
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assessing the validity responsiveness and meaningfulness of the hidradenitis suppurativa Clinical response hiscr as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P < 0·001). Improvements of all PROs in HiSCR achievers exceeded the respective meaningful improvement thresholds. Conclusions In patients with HS with ≥ 3 ANs, HiSCR achievers had significant improvements in physician-rated and patient-reported HS disease severity and impact. HiSCR is a valid and meaningful Endpoint for assessing HS treatment effectiveness in controlling inflammatory manifestations in this population.
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Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P
Yihua Gu - One of the best experts on this subject based on the ideXlab platform.
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hiscr hidradenitis suppurativa Clinical response a novel Clinical Endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo controlled portion of a phase 2 adalimumab study
Journal of The European Academy of Dermatology and Venereology, 2016Co-Authors: Alexa B. Kimball, Yihua Gu, Murali Sundaram, Jeffrey M Sobell, Christos C Zouboulis, David A Williams, H D Teixeira, Gregor B. E. JemecAbstract:Background Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Objective Evaluate the novel, validated Endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. Methods Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). Results The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. Conclusion HiSCR was more responsive to change than HS-PGA Response in this subpopulation.
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assessing the validity responsiveness and meaningfulness of the hidradenitis suppurativa Clinical response hiscr as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P < 0·001). Improvements of all PROs in HiSCR achievers exceeded the respective meaningful improvement thresholds. Conclusions In patients with HS with ≥ 3 ANs, HiSCR achievers had significant improvements in physician-rated and patient-reported HS disease severity and impact. HiSCR is a valid and meaningful Endpoint for assessing HS treatment effectiveness in controlling inflammatory manifestations in this population.
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Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the Clinical Endpoint for hidradenitis suppurativa treatment
British Journal of Dermatology, 2014Co-Authors: Alexa B. Kimball, Gregor B. E. Jemec, Min Yang, Andrew Kageleiry, James Signorovitch, Martin M. Okun, Yihua Gu, K. Wang, Parvez Mulani, Murali SundaramAbstract:Summary Background Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture Clinical improvement in hidradenitis suppurativa (HS) can be improved. Objectives This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful Clinical Endpoint for HS treatment. Methods Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test–retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed. Results Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test–retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between −0·61 and −0·27, all P
Viswanath Devanarayan - One of the best experts on this subject based on the ideXlab platform.
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Comparison of RNA-seq and microarray-based models for Clinical Endpoint prediction
Genome Biology, 2015Co-Authors: Wenqian Zhang, Jean Thierry-mieg, Danielle Thierry-mieg, Cesare Furlanello, Falk Hertwig, Viswanath Devanarayan, Ying Yu, Jian Wang, Jie ChengAbstract:BackgroundGene expression profiling is being widely applied in cancer research to identify biomarkers for Clinical Endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for Clinical Endpoint prediction using neuroblastoma as a model.ResultsWe generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting Clinical Endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six Clinical Endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the Clinical Endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models.ConclusionsWe demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in Clinical Endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in Clinical practice.
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comparison of rna seq and microarray based models for Clinical Endpoint prediction
Genome Biology, 2015Co-Authors: Wenqian Zhang, Cesare Furlanello, Falk Hertwig, Ying Yu, Jian Wang, Jean Thierrymieg, Wenwei Zhang, Danielle Thierrymieg, Viswanath DevanarayanAbstract:Background: Gene expression profiling is being widely applied in cancer research to identify biomarkers for Clinical Endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarraybased classifiers in this MAQC-III/SEQC study for Clinical Endpoint prediction using neuroblastoma as a model. Results: We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting Clinical Endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six Clinical Endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the Clinical Endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. (Continued on next page)
