74 research outputs found
Patch-based Convolutional Neural Network for Whole Slide Tissue Image Classification
Convolutional Neural Networks (CNN) are state-of-the-art models for many
image classification tasks. However, to recognize cancer subtypes
automatically, training a CNN on gigapixel resolution Whole Slide Tissue Images
(WSI) is currently computationally impossible. The differentiation of cancer
subtypes is based on cellular-level visual features observed on image patch
scale. Therefore, we argue that in this situation, training a patch-level
classifier on image patches will perform better than or similar to an
image-level classifier. The challenge becomes how to intelligently combine
patch-level classification results and model the fact that not all patches will
be discriminative. We propose to train a decision fusion model to aggregate
patch-level predictions given by patch-level CNNs, which to the best of our
knowledge has not been shown before. Furthermore, we formulate a novel
Expectation-Maximization (EM) based method that automatically locates
discriminative patches robustly by utilizing the spatial relationships of
patches. We apply our method to the classification of glioma and non-small-cell
lung carcinoma cases into subtypes. The classification accuracy of our method
is similar to the inter-observer agreement between pathologists. Although it is
impossible to train CNNs on WSIs, we experimentally demonstrate using a
comparable non-cancer dataset of smaller images that a patch-based CNN can
outperform an image-based CNN
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses
Background: Mutations in the Otopetrin 1 gene (Otop1) in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP) family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence-and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH) subtype 1G (Ush1g), both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results: We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF), a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq) data in mouse and human embryonic stem (ES) cells combined with detection of CTCF-binding motifs. Conclusions: The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s) of Ush1g and Otop in developmental pathways
Common Limitations of Image Processing Metrics:A Picture Story
While the importance of automatic image analysis is continuously increasing,
recent meta-research revealed major flaws with respect to algorithm validation.
Performance metrics are particularly key for meaningful, objective, and
transparent performance assessment and validation of the used automatic
algorithms, but relatively little attention has been given to the practical
pitfalls when using specific metrics for a given image analysis task. These are
typically related to (1) the disregard of inherent metric properties, such as
the behaviour in the presence of class imbalance or small target structures,
(2) the disregard of inherent data set properties, such as the non-independence
of the test cases, and (3) the disregard of the actual biomedical domain
interest that the metrics should reflect. This living dynamically document has
the purpose to illustrate important limitations of performance metrics commonly
applied in the field of image analysis. In this context, it focuses on
biomedical image analysis problems that can be phrased as image-level
classification, semantic segmentation, instance segmentation, or object
detection task. The current version is based on a Delphi process on metrics
conducted by an international consortium of image analysis experts from more
than 60 institutions worldwide.Comment: This is a dynamic paper on limitations of commonly used metrics. The
current version discusses metrics for image-level classification, semantic
segmentation, object detection and instance segmentation. For missing use
cases, comments or questions, please contact [email protected] or
[email protected]. Substantial contributions to this document will be
acknowledged with a co-authorshi
Understanding metric-related pitfalls in image analysis validation
Validation metrics are key for the reliable tracking of scientific progress
and for bridging the current chasm between artificial intelligence (AI)
research and its translation into practice. However, increasing evidence shows
that particularly in image analysis, metrics are often chosen inadequately in
relation to the underlying research problem. This could be attributed to a lack
of accessibility of metric-related knowledge: While taking into account the
individual strengths, weaknesses, and limitations of validation metrics is a
critical prerequisite to making educated choices, the relevant knowledge is
currently scattered and poorly accessible to individual researchers. Based on a
multi-stage Delphi process conducted by a multidisciplinary expert consortium
as well as extensive community feedback, the present work provides the first
reliable and comprehensive common point of access to information on pitfalls
related to validation metrics in image analysis. Focusing on biomedical image
analysis but with the potential of transfer to other fields, the addressed
pitfalls generalize across application domains and are categorized according to
a newly created, domain-agnostic taxonomy. To facilitate comprehension,
illustrations and specific examples accompany each pitfall. As a structured
body of information accessible to researchers of all levels of expertise, this
work enhances global comprehension of a key topic in image analysis validation.Comment: Shared first authors: Annika Reinke, Minu D. Tizabi; shared senior
authors: Paul F. J\"ager, Lena Maier-Hei
Federated learning enables big data for rare cancer boundary detection.
Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing
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