Improving Interpretability for Computer-aided Diagnosis tools on Whole Slide Imaging with Multiple Instance Learning and Gradient-based Explanations

Deep learning methods are widely used for medical applications to assist medical doctors in their daily routines. While performances reach expert's level, interpretability (highlight how and what a trained model learned and why it makes a specific decision) is the next important challenge that deep learning methods need to answer to be fully integrated in the medical field. In this paper, we address the question of interpretability in the context of whole slide images (WSI) classification. We formalize the design of WSI classification architectures and propose a piece-wise interpretability approach, relying on gradient-based methods, feature visualization and multiple instance learning context. We aim at explaining how the decision is made based on tile level scoring, how these tile scores are decided and which features are used and relevant for the task. After training two WSI classification architectures on Camelyon-16 WSI dataset, highlighting discriminative features learned, and validating our approach with pathologists, we propose a novel manner of computing interpretability slide-level heat-maps, based on the extracted features, that improves tile-level classification performances by more than 29% for AUC.Comment: 8 pages (references excluded), 3 figures, presented in iMIMIC Workshop at MICCAI 202

Responses of soil cellulolytic fungal communities to elevated atmospheric CO 2 are complex and variable across five ecosystems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86979/1/j.1462-2920.2011.02548.x.pd

Beta-synemin expression in cardiotoxin-injected rat skeletal muscle

Background: β-synemin was originally identified in humans as an α-dystrobrevin-binding protein through a yeast two-hybrid screen using an amino acid sequence derived from exons 1 through 16 of α-dystrobrevin, a region common to both α-dystrobrevin-1 and -2. α-Dystrobrevin-1 and -2 are both expressed in muscle and co-localization experiments have determined which isoform preferentially functions with β-synemin in vivo. The aim of our study is to show whether each α-dystrobrevin isoform has the same affinity for β-synemin or whether one of the isoforms preferentially functions with β-synemin in muscle. Methods: The two α-dystrobrevin isoforms (-1 and -2) and β-synemin were localized in regenerating rat tibialis anterior muscle using immunoprecipitation, immunohistochemical and immunoblot analyses. Immunoprecipitation and co-localization studies for α-dystrobrevin and β-synemin were performed in regenerating muscle following cardiotoxin injection. Protein expression was then compared to that of developing rat muscle using immunoblot analysis.Results: With an anti-α-dystrobrevin antibody, β-synemin co-immunoprecipitated with α-dystrobrevin whereas with an anti-β-synemin antibody, α-dystrobrevin-1 (rather than the -2 isoform) preferentially co-immunoprecipitated with β-synemin. Immunohistochemical experiments show that β-synemin and α-dystrobrevin co-localize in rat skeletal muscle. In regenerating muscle, β-synemin is first expressed at the sarcolemma and in the cytoplasm at day 5 following cardiotoxin injection. Similarly, β-synemin and α-dystrobrevin-1 are detected by immunoblot analysis as weak bands by day 7. In contrast, immunoblot analysis shows that α-dystrobrevin-2 is expressed as early as 1 day post-injection in regenerating muscle. These results are similar to that of developing muscle. For example, in embryonic rats, immunoblot analysis shows that β-synemin and α-dystrobevin-1 are weakly expressed in developing lower limb muscle at 5 days post-birth, while α-dystrobrevin-2 is detectable before birth in 20-day post-fertilization embryos. Conclusion: Our results clearly show that β-synemin expression correlates with that of α-dystrobrevin-1, suggesting that β-synemin preferentially functions with α-dystrobrevin-1 in vivo and that these proteins are likely to function coordinately to play a vital role in developing and regenerating muscle

Common bacterial responses in six ecosystems exposed to 10 years of elevated atmospheric carbon dioxide

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91149/1/j.1462-2920.2011.02695.x.pd

Protist diversity on a nature reserve in NW England − with particular reference to their role in soil biogenic silicon pools

Soil protists play fundamental roles in many earth system processes, yet we are only beginning to understand the true diversity of the organisms involved. In this study we used conventional (microscopy-based) methods to characterise the diversity and estimate protist population sizes in soils from a variety of distinct habitats within Mere Sands Wood nature reserve in NW England. We produced population size data for over ninety soil protists belonging to two major eukaryotic functional groups: testate amoebae (TA) and diatoms, adding substantial ‘cryptic diversity’ to the nature reserves recorded biota. From these population size data we estimated relative contributions of TA and diatoms to soil biogenic silicon (BSi) pools and found significant correlations between taxon richness and the TA and diatom Si pool. This could indicate that protist functional diversity can influence terrestrial BSi pools, especially in early successional plant communities where TA and diatoms can potentially increase Si mineralisation and/or create Si ‘hot spots’ and hence, the biological availability of this element for subsequent plant uptake. TA were particularly abundant in mor humus type soils further supporting the idea that they could be important players in nutrient cycling in such soils. Overall, we demonstrate this is a useful approach in order to start to attempt to estimate the role of protists in the Si cycle and other ecological processes

Functional Myogenic Engraftment from Mouse iPS Cells

Direct reprogramming of adult fibroblasts to a pluripotent state has opened new possibilities for the generation of patient- and disease-specific stem cells. However the ability of induced pluripotent stem (iPS) cells to generate tissue that mediates functional repair has been demonstrated in very few animal models of disease to date. Here we present the proof of principle that iPS cells may be used effectively for the treatment of muscle disorders. We combine the generation of iPS cells with conditional expression of Pax7, a robust approach to derive myogenic progenitors. Transplantation of Pax7-induced iPS-derived myogenic progenitors into dystrophic mice results in extensive engraftment, which is accompanied by improved contractility of treated muscles. These findings demonstrate the myogenic regenerative potential of iPS cells and provide rationale for their future therapeutic application for muscular dystrophies