PatternMarkers & GWCoGAPS for novel data-driven biomarkers via whole transcriptome NMF.
CONCLUSIONS
Non-negative Matrix Factorization (NMF) algorithms associate gene expression with biological processes (e.g. time-course dynamics or disease subtypes). Compared with univariate associations, the relative weights of NMF solutions can obscure biomarkers. Therefore, we developed a novel patternMarkers statistic to extract genes for biological validation and enhanced visualization of NMF results. Finding novel and unbiased gene markers with patternMarkers requires whole-genome data. Therefore, we also developed Genome-Wide CoGAPS Analysis in Parallel Sets (GWCoGAPS), the first robust whole genome Bayesian NMF using the sparse, MCMC algorithm, CoGAPS. Additionally, a manual version of the GWCoGAPS algorithm contains analytic and visualization tools including patternMatcher, a Shiny web application. The decomposition in the manual pipeline can be replaced with any NMF algorithm, for further generalization of the software. Using these tools, we find granular brain-region and cell-type specific signatures with corresponding biomarkers in GTEx data, illustrating GWCoGAPS and patternMarkers ascertainment of data-driven biomarkers from whole-genome data.


METHODS
PatternMarkers & GWCoGAPS are in the CoGAPS Bioconductor package (3.5) under the GPL license.


BACKGROUND
gsteinobrien@jhmi.edu or ccolantu@jhmi.edu or ejfertig@jhmi.edu.


BACKGROUND
Supplementary data are available at Bioinformatics online.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Lieber Institute for Brain Development, Baltimore, MD, USA.
Genevieve L
GL
Stein-O'Brien
Department of Oncology and Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jacob L
JL
Carey
Department of Oncology and Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Wai Shing
WS
Lee
Department of Oncology and Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Michael
M
Considine
Department of Oncology and Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Vavilov Institute of General Genetics, Moscow, Russia.|Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russia.
Alexander V
AV
Favorov
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Emily
E
Flam
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Theresa
T
Guo
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Sijia
S
Li
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Luigi
L
Marchionni
Department of Mathematics and Statistics, The College of New Jersey, Ewing Township, NJ, USA.
Thomas
T
Sherman
Department of Mathematics and Statistics, The College of New Jersey, Ewing Township, NJ, USA.
Shawn
S
Sivy
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Daria A
DA
Gaykalova
Lieber Institute for Brain Development, Baltimore, MD, USA.
Ronald D
RD
McKay
Department of Mathematics and Statistics, The College of New Jersey, Ewing Township, NJ, USA.
Michael F
MF
Ochs
Department of Neurology and Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Institute for Genome Sciences, University of Maryland School of Medicine.
Carlo
C
Colantuoni
Department of Oncology and Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Elana J
EJ
Fertig
D000465:Algorithms; D001499:Bayes Theorem; D015415:Biomarkers; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D017423:Sequence Analysis, RNA / Q000379:methods; D012984:Software
D015415:Biomarkers