104 research outputs found
Artificial intelligence in histopathology image analysis for cancer precision medicine
In recent years, there have been rapid advancements in the field of computational
pathology. This has been enabled through the adoption of digital pathology
workflows that generate digital images of histopathological slides, the publication
of large data sets of these images and improvements in computing infrastructure.
Objectives in computational pathology can be subdivided into two categories,
first the automation of routine workflows that would otherwise be performed by
pathologists and second the addition of novel capabilities. This thesis focuses on
the development, application, and evaluation of methods in this second category,
specifically the prediction of gene expression from pathology images and the
registration of pathology images among each other.
In Study I, we developed a computationally efficient cluster-based technique to
perform transcriptome-wide predictions of gene expression in prostate cancer
from H&E-stained whole-slide-images (WSIs). The suggested method
outperforms several baseline methods and is non-inferior to single-gene CNN
predictions, while reducing the computational cost with a factor of approximately
300. We included 15,586 transcripts that encode proteins in the analysis and
predicted their expression with different modelling approaches from the WSIs. In
a cross-validation, 6,618 of these predictions were significantly associated with
the RNA-seq expression estimates with FDR-adjusted p-values <0.001. Upon
validation of these 6,618 expression predictions in a held-out test set, the
association could be confirmed for 5,419 (81.9%). Furthermore, we demonstrated
that it is feasible to predict the prognostic cell-cycle progression score with a
Spearman correlation to the RNA-seq score of 0.527 [0.357, 0.665].
The objective of Study II is the investigation of attention layers in the context of
multiple-instance-learning for regression tasks, exemplified by a simulation study
and gene expression prediction. We find that for gene expression prediction, the
compared methods are not distinguishable regarding their performance, which
indicates that attention mechanisms may not be superior to weakly supervised
learning in this context.
Study III describes the results of the ACROBAT 2022 WSI registration challenge,
which we organised in conjunction with the MICCAI 2022 conference. Participating
teams were ranked on the median 90th percentile of distances between
registered and annotated target landmarks. Median 90th percentiles for eight
teams that were eligible for ranking in the test set consisting of 303 WSI pairs
ranged from 60.1 µm to 15,938.0 µm. The best performing method therefore has a
score slightly below the median 90th percentile of distances between first and
second annotator of 67.0 µm.
Study IV describes the data set that we published to facilitate the ACROBAT
challenge. The data set is available publicly through the Swedish National Data
Service SND and consists of 4,212 WSIs from 1,153 breast cancer patients.
Study V is an example of the application of WSI registration for computational
pathology. In this study, we investigate the possibility to register invasive cancer
annotations from H&E to KI67 WSIs and then subsequently train cancer detection
models. To this end, we compare the performance of models optimised with
registered annotations to the performance of models that were optimised with
annotations generated for the KI67 WSIs. The data set consists of 272 female
breast cancer cases, including an internal test set of 54 cases. We find that in this
test set, the performance of both models is not distinguishable regarding
performance, while there are small differences in model calibration
Experiments in randomly agitated granular assemblies close to the jamming transition
We present here the preliminary results obtained for two experiments on
randomly agitated granular assemblies using a novel way of shaking. First we
discuss the transport properties of a 2D model system undergoing classical
shaking that show the importance of large scale dynamics for this type of
agitation and offer a local view of the microscopic motions of a grain. We then
develop a new way of vibrating the system allowing for random accelerations
smaller than gravity. Using this method we study the evolution of the free
surface as well as results from a light scattering method for a 3D model
system. The final aim of these experiments is to investigate the ideas of
effective temperature on the one hand as a function of inherent states and on
the other hand using fluctuation dissipation relations.Comment: Contribution to the volume "Unifying Concepts in Granular Media and
Glasses", edt.s A. Coniglio, A. Fierro, H.J. Herrmann and M. Nicodem
Towards Principled Responsible Research and Innovation: Employing the Difference Principle in Funding Decisions
Responsible Research and Innovation (RRI) has emerged as a science policy framework that attempts to import broad social values into technological innovation processes whilst supporting institutional decision-making under conditions of uncertainty and ambiguity. When looking at RRI from a ‘principled’ perspective, we consider responsibility and justice to be important cornerstones of the framework. The main aim of this article is to suggest a method of realising these principles through the application of a limited Rawlsian Difference Principle in the distribution of public funds for research and innovation.
There are reasons why the world's combined innovative capacity has spewed forth iPhones and space shuttles but not yet managed to produce clean energy or universal access to clean water. (Stilgoe 2013, xii)
I derive great optimism from empathy's evolutionary antiquity. It makes it a robust trait that will develop in virtually every human being so that society can count on it and try to foster and grow it. It is a human universal.
(de Waal 2009, 209)
Responsible Research and Innovation (RRI) has emerged as a science policy framework that attempts to import broad social values into technological innovation processes whilst supporting institutional decision-making under conditions of uncertainty and ambiguity. In this respect, RRI re-focuses technological governance from standard debates on risks to discussions about the ethical stewardship of innovation.
This is a radical step in Science & Technology (S&T) policy as it lifts the non-quantifiable concept of values into the driving seat of decision-making. The focus of innovation then goes beyond product considerations to include the processes and – importantly – the purposes of innovation (Owen et al. 2013, 34). Shared public values are seen as the cornerstone of the new RRI framework, while market mechanisms and risk-based regulations are of a secondary order.
What are the values that could drive RRI? There are different approaches to the identification of public values. They can be located in democratically agreed processes and commitments (such as European Union treaties and policy statements) or they can be developed organically via public engagement processes. Both approaches have advantages and disadvantages. For instance, although constitutional values can be regarded as democratically legitimate, their application to specific technological fields can be difficult or ambiguous (Schroeder and Rerimassie 2015). On the other hand, public engagement can accurately reflect stakeholder values but is not necessarily free from bias and lobbyist agenda setting.
We argue that if RRI is to be more successful in resolving policy dilemmas arising from poorly described and uncertain technological impacts, basic universal principles need to be evoked and applied.
When looking at RRI from a ‘principled’ perspective, we consider responsibility and justice to be important cornerstones of the framework. One could describe them in the following manner:
Research and innovation should be conducted responsibly.
Publicly funded research and innovation should be focused fairly on socially beneficial targets. Research and innovation should promote and not hinder social justice.
The main aim of this article is to suggest a method of realising these principles through the application of a limited Rawlsian Difference Principle in the distribution of public funds for research and innovation.
This paper is in three parts. The first part discusses the above principles and introduces the Rawlsian Difference Principle. The second part identifies how RRI is currently applied by public funding bodies. The third part discusses the operationalisation of the Rawlsian Difference Principle in responsible funding decisions
Predicting Molecular Phenotypes from Histopathology Images: A Transcriptome-Wide Expression-Morphology Analysis in Breast Cancer
Molecular profiling is central in cancer precision medicine but remains costly and is based on tumor average profiles. Morphologic patterns observable in histopathology sections from tumors are determined by the underlying molecular phenotype and therefore have the potential to be exploited for prediction of molecular phenotypes. We report here the first transcriptome-wide expression-morphology (EMO) analysis in breast cancer, where individual deep convolutional neural networks were optimized and validated for prediction of mRNA expression in 17,695 genes from hematoxylin and eosin-stained whole slide images. Predicted expressions in 9,334 (52.75%) genes were significantly associated with RNA sequencing estimates. We also demonstrated successful prediction of an mRNA-based proliferation score with established clinical value. The results were validated in independent internal and external test datasets. Predicted spatial intratumor variabilities in expression were validated through spatial transcriptomics profiling. These results suggest that EMO provides a cost-efficient and scalable approach to predict both tumor average and intratumor spatial expression from histopathology images.Significance: Transcriptome-wide expression morphology deep learning analysis enables prediction of mRNA expression and proliferation markers from routine histopathology whole slide images in breast cancer
ACROBAT -- a multi-stain breast cancer histological whole-slide-image data set from routine diagnostics for computational pathology
The analysis of FFPE tissue sections stained with haematoxylin and eosin
(H&E) or immunohistochemistry (IHC) is an essential part of the pathologic
assessment of surgically resected breast cancer specimens. IHC staining has
been broadly adopted into diagnostic guidelines and routine workflows to
manually assess status and scoring of several established biomarkers, including
ER, PGR, HER2 and KI67. However, this is a task that can also be facilitated by
computational pathology image analysis methods. The research in computational
pathology has recently made numerous substantial advances, often based on
publicly available whole slide image (WSI) data sets. However, the field is
still considerably limited by the sparsity of public data sets. In particular,
there are no large, high quality publicly available data sets with WSIs of
matching IHC and H&E-stained tissue sections. Here, we publish the currently
largest publicly available data set of WSIs of tissue sections from surgical
resection specimens from female primary breast cancer patients with matched
WSIs of corresponding H&E and IHC-stained tissue, consisting of 4,212 WSIs from
1,153 patients. The primary purpose of the data set was to facilitate the
ACROBAT WSI registration challenge, aiming at accurately aligning H&E and IHC
images. For research in the area of image registration, automatic quantitative
feedback on registration algorithm performance remains available through the
ACROBAT challenge website, based on more than 37,000 manually annotated
landmark pairs from 13 annotators. Beyond registration, this data set has the
potential to enable many different avenues of computational pathology research,
including stain-guided learning, virtual staining, unsupervised pre-training,
artefact detection and stain-independent models
The ACROBAT 2022 Challenge: Automatic Registration Of Breast Cancer Tissue
The alignment of tissue between histopathological whole-slide-images (WSI) is
crucial for research and clinical applications. Advances in computing, deep
learning, and availability of large WSI datasets have revolutionised WSI
analysis. Therefore, the current state-of-the-art in WSI registration is
unclear. To address this, we conducted the ACROBAT challenge, based on the
largest WSI registration dataset to date, including 4,212 WSIs from 1,152
breast cancer patients. The challenge objective was to align WSIs of tissue
that was stained with routine diagnostic immunohistochemistry to its
H&E-stained counterpart. We compare the performance of eight WSI registration
algorithms, including an investigation of the impact of different WSI
properties and clinical covariates. We find that conceptually distinct WSI
registration methods can lead to highly accurate registration performances and
identify covariates that impact performances across methods. These results
establish the current state-of-the-art in WSI registration and guide
researchers in selecting and developing methods
Contrasting Population Structures of Two Vectors of African Trypanosomoses in Burkina Faso: Consequences for Control
Tsetse flies are insects that transmit trypanosomes to humans (sleeping sickness) and animals (nagana). Controlling these vectors is a very efficient way to control these diseases. In Burkina Faso, a tsetse eradication campaign is presently targeting the northern part of the Mouhoun River Basin. To attain this objective, the approach has to be area-wide, i.e. the control effort targets an entire pest population within a circumscribed area. To assess the level of this isolation, we studied the genetic structure of Glossina palpalis gambiensis and Glossina tachinoides populations in the target area and in the adjacent river basins of the Comoé, the Niger and the Sissili River Basins. Our results suggest an absence of strong genetic isolation of the target populations. We therefore recommend establishing permanent buffer zones between the Mouhoun and the other river basin(s) to prevent reinvasion. This kind of study may be extended to other areas on other tsetse species
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Rapport d’identification d’essence, Poutre avec marque de marchand, Maison Erasme à Anderlecht
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