N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes
Schissler, A. Grant
Zhang, Hao Helen
Lussier, Yves A.
AffiliationUniv Arizona, Ctr Biomed Informat & Biostat
Univ Arizona, Inst Bio5
Univ Arizona, Dept Med
Univ Arizona, Grad Interdisciplinary Program Stat
Univ Arizona, Dept Math
Univ Arizona, Canc Ctr
Head and neck squamous cell carcinomas (HNSCCs)
MetadataShow full item record
PublisherBIOMED CENTRAL LTD
CitationN-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes 2017, 10 (S1) BMC Medical Genomics
JournalBMC Medical Genomics
Rights© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractBackground: Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient. Although, both methods uncover concordantly dysregulated pathways, they are not designed to detect dysregulated pathways with up- and down-regulated genes (bidirectional dysregulation) that are ubiquitous in biological systems. Results: We developed N-of-1-pathways MixEnrich, a mixture model followed by a gene set enrichment test, to uncover bidirectional and concordantly dysregulated pathways one patient at a time. We assess its accuracy in a comprehensive simulation study and in a RNA-Seq data analysis of head and neck squamous cell carcinomas (HNSCCs). In presence of bidirectionally dysregulated genes in the pathway or in presence of high background noise, MixEnrich substantially outperforms previous single-subject transcriptome analysis methods, both in the simulation study and the HNSCCs data analysis (ROC Curves; higher true positive rates; lower false positive rates). Bidirectional and concordant dysregulated pathways uncovered by MixEnrich in each patient largely overlapped with the quasi-gold standard compared to other single-subject and cohort-based transcriptome analyses. Conclusion: The greater performance of MixEnrich presents an advantage over previous methods to meet the promise of providing accurate personal transcriptome analysis to support precision medicine at point of care.
NoteOpen Access Journal.
VersionFinal published version
SponsorsNIH [K22LM008308]; NSF [DMS-1309507, DMS-1418172]; University of Arizona Center for Biomedical Informatics and Biostatistics; NCI of the University of Arizona Cancer Center [P30CA023074]
CollectionsUA Faculty Publications
- kMEn: Analyzing noisy and bidirectional transcriptional pathway responses in single subjects.
- Authors: Li Q, Schissler AG, Gardeux V, Berghout J, Achour I, Kenost C, Li H, Zhang HH, Lussier YA
- Issue date: 2017 Feb
- Dynamic changes of RNA-sequencing expression for precision medicine: N-of-1-pathways Mahalanobis distance within pathways of single subjects predicts breast cancer survival.
- Authors: Schissler AG, Gardeux V, Li Q, Achour I, Li H, Piegorsch WW, Lussier YA
- Issue date: 2015 Jun 15
- 'N-of-1-pathways' unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine.
- Authors: Gardeux V, Achour I, Li J, Maienschein-Cline M, Li H, Pesce L, Parinandi G, Bahroos N, Winn R, Foster I, Garcia JG, Lussier YA
- Issue date: 2014 Nov-Dec
- Towards a PBMC "virogram assay" for precision medicine: Concordance between ex vivo and in vivo viral infection transcriptomes.
- Authors: Gardeux V, Bosco A, Li J, Halonen MJ, Jackson D, Martinez FD, Lussier YA
- Issue date: 2015 Jun
- A genome-by-environment interaction classifier for precision medicine: personal transcriptome response to rhinovirus identifies children prone to asthma exacerbations.
- Authors: Gardeux V, Berghout J, Achour I, Schissler AG, Li Q, Kenost C, Li J, Shang Y, Bosco A, Saner D, Halonen MJ, Jackson DJ, Li H, Martinez FD, Lussier YA
- Issue date: 2017 Nov 1