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a tma de-arraying method for high throughput biomarker discovery in tissue researchtma de-arraying方法高通量生物标志物发现在组织研究
A TMA De-Arraying Method for High Throughput
Biomarker Discovery in Tissue Research
Yinhai Wang*, Kienan Savage, Claire Grills, Andrena McCavigan, Jacqueline A. James, Dean A. Fennell,
Peter W. Hamilton
Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, United Kingdom
Abstract
Background: Tissue MicroArrays (TMAs) represent a potential high-throughput platform for the analysis and discovery of
tissue biomarkers. As TMA slides are produced manually and subject to processing and sectioning artefacts, the layout of
TMA cores on the final slide and subsequent digital scan (TMA digital slide) is often disturbed making it difficult to associate
cores with their original position in the planned TMA map. Additionally, the individual cores can be greatly altered and
contain numerous irregularities such as missing cores, grid rotation and stretching. These factors demand the development
of a robust method for de-arraying TMAs which identifies each TMA core, and assigns them to their appropriate coordinates
on the constructed TMA slide.
Methodology: This study presents a robust TMA de-arraying method consisting of three functional phases: TMA core
segmentation, gridding and mapping. The segmentation of TMA cores uses a set of morphological operations to identify
each TMA core. Gridding then utilises a Delaunay Triangulation based method to find the row and column indices of each
TMA core. Finally, mapping correlates each TMA core from a high resolution TMA whole slide image with its name within a
TMAMap.
Conclusion: This study describes a genuine robust TMA de-arraying algorithm for the rapid identification of TMA cores from
digital slides. The result of this de-arraying algorithm allows the easy partition of each TMA core for further processing.
Based on a test group of 19 TMA slides (3129 cores), 99.84% of cores
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