Shaped 3D singular spectrum analysis for quantifying gene expression, with application to the early zebrafish embryo.
Recent progress in microscopy technologies, biological markers, and automated processing methods is making possible the development of gene expression atlases at cellular-level resolution over whole embryos. Raw data on gene expression is usually very noisy. This noise comes from both experimental (technical/methodological) and true biological sources (from stochastic biochemical processes). In addition, the cells or nuclei being imaged are irregularly arranged in 3D space. This makes the processing, extraction, and study of expression signals and intrinsic biological noise a serious challenge for 3D data, requiring new computational approaches. Here, we present a new approach for studying gene expression in nuclei located in a thick layer around a spherical surface. The method includes depth equalization on the sphere, flattening, interpolation to a regular grid, pattern extraction by Shaped 3D singular spectrum analysis (SSA), and interpolation back to original nuclear positions. The approach is demonstrated on several examples of gene expression in the zebrafish egg (a model system in vertebrate development). The method is tested on several different data geometries (e.g., nuclear positions) and different forms of gene expression patterns. Fully 3D datasets for developmental gene expression are becoming increasingly available; we discuss the prospects of applying 3D-SSA to data processing and analysis in this growing field.
Faculty of Mathematics and Mechanics, St. Petersburg State University, Universitetsky Pr. 28, St. Peterhof, St. Petersburg 198504, Russia.
Alex
A
Shlemov
Faculty of Mathematics and Mechanics, St. Petersburg State University, Universitetsky Pr. 28, St. Peterhof, St. Petersburg 198504, Russia.
Nina
N
Golyandina
Mathematics Department, British Columbia Institute of Technology, 3700 Willingdon Avenue, Burnaby, BC, Canada V5G 3H2.
David
D
Holloway
Computer Science and CEWIT, SUNY Stony Brook, 1500 Stony Brook Road, Stony Brook, NY 11794, USA ; The Sechenov Institute of Evolutionary Physiology & Biochemistry, Torez Pr. 44, St. Petersburg 194223, Russia.
Alexander
A
Spirov
D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*