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Register a new userPathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis
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Cancer diagnosis, prognosis, and therapeutic response predictions are based on morphological information from histology slides and molecular profiles from genomic data. However, most deep learning-based objective outcome prediction and grading paradigms are based on histology or genomics alone and do not make use of the complementary information in an intuitive manner. In this work, we propose Pathomic Fusion, an interpretable strategy for end-to-end multimodal fusion of histology image and genomic (mutations, CNV, RNA-Seq) features for survival outcome prediction. Our approach models pairwise feature interactions across modalities by taking the Kronecker product of unimodal feature representations and controls the expressiveness of each representation via a gating-based attention mechanism. Following supervised learning, we are able to interpret and saliently localize features across each modality, and understand how feature importance shifts when conditioning on multimodal input. We validate our approach using glioma and clear cell renal cell carcinoma datasets from the Cancer Genome Atlas (TCGA), which contains paired whole-slide image, genotype, and transcriptome data with ground truth survival and histologic grade labels. In a 15-fold cross-validation, our results demonstrate that the proposed multimodal fusion paradigm improves prognostic determinations from ground truth grading and molecular subtyping, as well as unimodal deep networks trained on histology and genomic data alone. The proposed method establishes insight and theory on how to train deep networks on multimodal biomedical data in an intuitive manner, which will be useful for other problems in medicine that seek to combine heterogeneous data streams for understanding diseases and predicting response and resistance to treatment.
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Motivation: We introduce TRONCO (TRanslational ONCOlogy), an open-source R package that implements the state-of-the-art algorithms for the inference of cancer progression models from (epi)genomic mutational profiles. TRONCO can be used to extract population-level models describing the trends of accumulation of alterations in a cohort of cross-sectional samples, e.g., retrieved from publicly available databases, and individual-level models that reveal the clonal evolutionary history in single cancer patients, when multiple samples, e.g., multiple biopsies or single-cell sequencing data, are available. The resulting models can provide key hints in uncovering the evolutionary trajectories of cancer, especially for precision medicine or personalized therapy. Availability: TRONCO is released under the GPL license, it is hosted in the Software section at http://bimib.disco.unimib.it/ and archived also at bioconductor.org. Contact: [email protected]
Current Computer-Aided Diagnosis (CAD) methods mainly depend on medical images. The clinical information, which usually needs to be considered in practical clinical diagnosis, has not been fully employed in CAD. In this paper, we propose a novel deep learning-based method for fusing Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) images and clinical information for diagnostic tasks. Two paths of neural layers are performed to extract image features and clinical features, respectively, and at the same time clinical features are employed as the attention to guide the extraction of image features. Finally, these two modalities of features are concatenated to make decisions. We evaluate the proposed method on its applications to Alzheimers disease diagnosis, mild cognitive impairment converter prediction and hepatic microvascular invasion diagnosis. The encouraging experimental results prove the values of the image feature extraction guided by clinical features and the concatenation of two modalities of features for classification, which improve the performance of diagnosis effectively and stably.
When analyzing the genome, researchers have discovered that proteins bind to DNA based on certain patterns of the DNA sequence known as motifs. However, it is difficult to manually construct motifs due to their complexity. Recently, externally learned memory models have proven to be effective methods for reasoning over inputs and supporting sets. In this work, we present memory matching networks (MMN) for classifying DNA sequences as protein binding sites. Our model learns a memory bank of encoded motifs, which are dynamic memory modules, and then matches a new test sequence to each of the motifs to classify the sequence as a binding or nonbinding site.
Despite numerous mass extinctions in the Phanerozoic eon, the overall trend in biodiversity evolution was not blocked and the life has never been wiped out. Almost all possible catastrophic events (large igneous province, asteroid impact, climate change, regression and transgression, anoxia, acidification, sudden release of methane clathrate, multi-cause etc.) have been proposed to explain the mass extinctions. However, we should, above all, clarify at what timescale and at what possible levels should we explain the mass extinction? Even though the mass extinctions occurred at short-timescale and at the species level, we reveal that their cause should be explained in a broader context at tectonic timescale and at both the molecular level and the species level. The main result in this paper is that the Phanerozoic biodiversity evolution has been explained by reconstructing the Sepkoski curve based on climatic, eustatic and genomic data. Consequently, we point out that the P-Tr extinction was caused by the tectonically originated climate instability. We also clarify that the overall trend of biodiversification originated from the underlying genome size evolution, and that the fluctuation of biodiversity originated from the interactions among the earths spheres. The evolution at molecular level had played a significant role for the survival of life from environmental disasters.
Breast cancer is one of the leading fatal disease worldwide with high risk control if early discovered. Conventional method for breast screening is x-ray mammography, which is known to be challenging for early detection of cancer lesions. The dense breast structure produced due to the compression process during imaging lead to difficulties to recognize small size abnormalities. Also, inter- and intra-variations of breast tissues lead to significant difficulties to achieve high diagnosis accuracy using hand-crafted features. Deep learning is an emerging machine learning technology that requires a relatively high computation power. Yet, it proved to be very effective in several difficult tasks that requires decision making at the level of human intelligence. In this paper, we develop a new network architecture inspired by the U-net structure that can be used for effective and early detection of breast cancer. Results indicate a high rate of sensitivity and specificity that indicate potential usefulness of the proposed approach in clinical use.
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