6,387 research outputs found
Prospects for Theranostics in Neurosurgical Imaging: Empowering Confocal Laser Endomicroscopy Diagnostics via Deep Learning
Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence
imaging technology that has the potential to increase intraoperative precision,
extend resection, and tailor surgery for malignant invasive brain tumors
because of its subcellular dimension resolution. Despite its promising
diagnostic potential, interpreting the gray tone fluorescence images can be
difficult for untrained users. In this review, we provide a detailed
description of bioinformatical analysis methodology of CLE images that begins
to assist the neurosurgeon and pathologist to rapidly connect on-the-fly
intraoperative imaging, pathology, and surgical observation into a
conclusionary system within the concept of theranostics. We present an overview
and discuss deep learning models for automatic detection of the diagnostic CLE
images and discuss various training regimes and ensemble modeling effect on the
power of deep learning predictive models. Two major approaches reviewed in this
paper include the models that can automatically classify CLE images into
diagnostic/nondiagnostic, glioma/nonglioma, tumor/injury/normal categories and
models that can localize histological features on the CLE images using weakly
supervised methods. We also briefly review advances in the deep learning
approaches used for CLE image analysis in other organs. Significant advances in
speed and precision of automated diagnostic frame selection would augment the
diagnostic potential of CLE, improve operative workflow and integration into
brain tumor surgery. Such technology and bioinformatics analytics lend
themselves to improved precision, personalization, and theranostics in brain
tumor treatment.Comment: See the final version published in Frontiers in Oncology here:
https://www.frontiersin.org/articles/10.3389/fonc.2018.00240/ful
INTEGRATIVE ANALYSIS OF OMICS DATA IN ADULT GLIOMA AND OTHER TCGA CANCERS TO GUIDE PRECISION MEDICINE
Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional omics genomic data to promote the understanding of gene signatures and somatic molecular alterations contributing to cancer progression and clinical outcomes. Following this motivation, my dissertation has been focused on the following three topics in translational genomics.
1) Characterization of transcriptomic plasticity and its association with the tumor microenvironment in glioblastoma (GBM). I have integrated transcriptomic, genomic, protein and clinical data to increase the accuracy of GBM classification, and identify the association between the GBM mesenchymal subtype and reduced tumorpurity, accompanied with increased presence of tumor-associated microglia. Then I have tackled the sole source of microglial as intrinsic tumor bulk but not their corresponding neurosphere cells through both transcriptional and protein level analysis using a panel of sphere-forming glioma cultures and their parent GBM samples.FurthermoreI have demonstrated my hypothesis through longitudinal analysis of paired primary and recurrent GBM samples that the phenotypic alterations of GBM subtypes are not due to intrinsic proneural-to-mesenchymal transition in tumor cells, rather it is intertwined with increased level of microglia upon disease recurrence. Collectively I have elucidated the critical role of tumor microenvironment (Microglia and macrophages from central nervous system) contributing to the intra-tumor heterogeneity and accurate classification of GBM patients based on transcriptomic profiling, which will not only significantly impact on clinical perspective but also pave the way for preclinical cancer research.
2) Identification of prognostic gene signatures that stratify adult diffuse glioma patientsharboring1p/19q co-deletions. I have compared multiple statistical methods and derived a gene signature significantly associated with survival by applying a machine learning algorithm. Then I have identified inflammatory response and acetylation activity that associated with malignant progression of 1p/19q co-deleted glioma. In addition, I showed this signature translates to other types of adult diffuse glioma, suggesting its universality in the pathobiology of other subset gliomas. My efforts on integrative data analysis of this highly curated data set usingoptimizedstatistical models will reflect the pending update to WHO classification system oftumorsin the central nervous system (CNS).
3) Comprehensive characterization of somatic fusion transcripts in Pan-Cancers. I have identified a panel of novel fusion transcripts across all of TCGA cancer types through transcriptomic profiling. Then I have predicted fusion proteins with kinase activity and hub function of pathway network based on the annotation of genetically mobile domains and functional domain architectures. I have evaluated a panel of in -frame gene fusions as potential driver mutations based on network fusion centrality hypothesis. I have also characterised the emerging complexity of genetic architecture in fusion transcripts through integrating genomic structure and somatic variants and delineating the distinct genomic patterns of fusion events across different cancer types. Overall my exploration of the pathogenetic impact and clinical relevance of candidate gene fusions have provided fundamental insights into the management of a subset of cancer patients by predicting the oncogenic signalling and specific drug targets encoded by these fusion genes.
Taken together, the translational genomic research I have conducted during my Ph.D. study will shed new light on precision medicine and contribute to the cancer research community. The novel classification concept, gene signature and fusion transcripts I have identified will address several hotly debated issues in translational genomics, such as complex interactions between tumor bulks and their adjacent microenvironments, prognostic markers for clinical diagnostics and personalized therapy, distinct patterns of genomic structure alterations and oncogenic events in different cancer types, therefore facilitating our understanding of genomic alterations and moving us towards the development of precision medicine
Unsupervised patient representations from clinical notes with interpretable classification decisions
We have two main contributions in this work: 1. We explore the usage of a
stacked denoising autoencoder, and a paragraph vector model to learn
task-independent dense patient representations directly from clinical notes. We
evaluate these representations by using them as features in multiple supervised
setups, and compare their performance with those of sparse representations. 2.
To understand and interpret the representations, we explore the best encoded
features within the patient representations obtained from the autoencoder
model. Further, we calculate the significance of the input features of the
trained classifiers when we use these pretrained representations as input.Comment: Accepted poster at NIPS 2017 Workshop on Machine Learning for Health
(https://ml4health.github.io/2017/
Classification methods for the development of genomic signatures from high-dimensional data
Personalized medicine is defined by the use of genomic signatures of patients to assign effective therapies. We present Classification by Ensembles from Random Partitions (CERP) for class prediction and apply CERP to genomic data on leukemia patients and to genomic data with several clinical variables on breast cancer patients. CERP performs consistently well compared to the other classification algorithms. The predictive accuracy can be improved by adding some relevant clinical/histopathological measurements to the genomic data
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