🍩 Database of Original & Non-Theoretical Uses of Topology
(found 7 matches in 0.00261s)
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Persistent Homology Index as a Robust Quantitative Measure of Immunohistochemical Scoring (2017)
Akihiro Takiyama, Takashi Teramoto, Hiroaki Suzuki, Katsushige Yamashiro, Shinya TanakaAbstract
Immunohistochemical data (IHC) plays an important role in clinical practice, and is typically gathered in a semi-quantitative fashion that relies on some degree of visual scoring. However, visual scoring by a pathologist is inherently subjective and manifests both intra-observer and inter-observer variability. In this study, we introduce a novel computer-aided quantification methodology for immunohistochemical scoring that uses the algebraic concept of persistent homology. Using 8 bit grayscale image data derived from 90 specimens of invasive ductal carcinoma of the breast, stained for the replicative marker Ki-67, we computed homology classes. These were then compared to nuclear grades and the Ki-67 labeling indices obtained by visual scoring. Three metrics for IHC staining were newly defined: Persistent Homology Index (PHI), center coordinates of positive and negative groups, and the sum of squares within groups (WSS). This study demonstrates that PHI, a novel index for immunohistochemical labeling using persistent homology, can produce highly similar data to that generated by a pathologist using visual evaluation. The potential benefits associated with our novel technology include both improved quantification and reproducibility. Since our method reflects cellularity and nuclear atypia, it carries a greater quantity of biologic data compared to conventional evaluation using Ki-67. -
Identification of Copy Number Aberrations in Breast Cancer Subtypes Using Persistence Topology (2015)
Javier Arsuaga, Tyler Borrman, Raymond Cavalcante, Georgina Gonzalez, Catherine ParkAbstract
DNA copy number aberrations (CNAs) are of biological and medical interest because they help identify regulatory mechanisms underlying tumor initiation and evolution. Identification of tumor-driving CNAs (driver CNAs) however remains a challenging task, because they are frequently hidden by CNAs that are the product of random events that take place during tumor evolution. Experimental detection of CNAs is commonly accomplished through array comparative genomic hybridization (aCGH) assays followed by supervised and/or unsupervised statistical methods that combine the segmented profiles of all patients to identify driver CNAs. Here, we extend a previously-presented supervised algorithm for the identification of CNAs that is based on a topological representation of the data. Our method associates a two-dimensional (2D) point cloud with each aCGH profile and generates a sequence of simplicial complexes, mathematical objects that generalize the concept of a graph. This representation of the data permits segmenting the data at different resolutions and identifying CNAs by interrogating the topological properties of these simplicial complexes. We tested our approach on a published dataset with the goal of identifying specific breast cancer CNAs associated with specific molecular subtypes. Identification of CNAs associated with each subtype was performed by analyzing each subtype separately from the others and by taking the rest of the subtypes as the control. Our results found a new amplification in 11q at the location of the progesterone receptor in the Luminal A subtype. Aberrations in the Luminal B subtype were found only upon removal of the basal-like subtype from the control set. Under those conditions, all regions found in the original publication, except for 17q, were confirmed; all aberrations, except those in chromosome arms 8q and 12q were confirmed in the basal-like subtype. These two chromosome arms, however, were detected only upon removal of three patients with exceedingly large copy number values. More importantly, we detected 10 and 21 additional regions in the Luminal B and basal-like subtypes, respectively. Most of the additional regions were either validated on an independent dataset and/or using GISTIC. Furthermore, we found three new CNAs in the basal-like subtype: a combination of gains and losses in 1p, a gain in 2p and a loss in 14q. Based on these results, we suggest that topological approaches that incorporate multiresolution analyses and that interrogate topological properties of the data can help in the identification of copy number changes in cancer. -
Topological Descriptors of Histology Images (2014)
Nikhil Singh, Heather D. Couture, J. S. Marron, Charles Perou, Marc NiethammerAbstract
The purpose of this study is to investigate architectural characteristics of cell arrangements in breast cancer histology images. We propose the use of topological data analysis to summarize the geometric information inherent in tumor cell arrangements. Our goal is to use this information as signatures that encode robust summaries of cell arrangements in tumor tissue as captured through histology images. In particular, using ideas from algebraic topology we construct topological descriptors based on cell nucleus segmentations such as persistency charts and Betti sequences. We assess their performance on the task of discriminating the breast cancer subtypes Basal, Luminal A, Luminal B and HER2. We demonstrate that the topological features contain useful complementary information to image-appearance based features that can improve discriminatory performance of classifiers. -
Extracting Insights From the Shape of Complex Data Using Topology (2013)
P. Y. Lum, G. Singh, A. Lehman, T. Ishkanov, M. Vejdemo-Johansson, M. Alagappan, J. Carlsson, G. CarlssonAbstract
This paper applies topological methods to study complex high dimensional data sets by extracting shapes (patterns) and obtaining insights about them. Our method combines the best features of existing standard methodologies such as principal component and cluster analyses to provide a geometric representation of complex data sets. Through this hybrid method, we often find subgroups in data sets that traditional methodologies fail to find. Our method also permits the analysis of individual data sets as well as the analysis of relationships between related data sets. We illustrate the use of our method by applying it to three very different kinds of data, namely gene expression from breast tumors, voting data from the United States House of Representatives and player performance data from the NBA, in each case finding stratifications of the data which are more refined than those produced by standard methods. -
Topological Analysis of Gene Expression Arrays Identifies High Risk Molecular Subtypes in Breast Cancer (2012)
Javier Arsuaga, Nils A. Baas, Daniel DeWoskin, Hideaki Mizuno, Aleksandr Pankov, Catherine ParkAbstract
Genomic technologies measure thousands of molecular signals with the goal of understanding complex biological processes. In cancer these molecular signals have been used to characterize disease subtypes, signaling pathways and to identify subsets of patients with specific prognosis. However molecular signals for any disease type are so vast and complex that novel mathematical approaches are required for further analyses. Persistent and computational homology provide a new method for these analyses. In our previous work we presented a new homology-based supervised classification method to identify copy number aberrations from comparative genomic hybridization arrays. In this work we first propose a theoretical framework for our classification method and second we extend our analysis to gene expression data. We analyze a published breast cancer data set and find that that our method can distinguish most, but not all, different breast cancer subtypes. This result suggests that specific relationships between genes, captured by our algorithm, help distinguish between breast cancer subtypes. We propose that topological methods can be used for the classification and clustering of gene expression profiles. -
Topology Based Data Analysis Identifies a Subgroup of Breast Cancers With a Unique Mutational Profile and Excellent Survival (2011)
Monica Nicolau, Arnold J. Levine, Gunnar CarlssonAbstract
High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER+) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER+ breast cancers. We denote the group as c-MYB+ breast cancer.