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Background: Type 1 diabetes (T1D) is a devastating disease with serious health complications. Early T1D biomarkers that could enable timely detection and prevention before the onset of clinical symptoms are paramount but currently unavailable. Despite their promise, omics approaches have so far failed to deliver such biomarkers, likely due to the fragmented nature of information obtained through the single omics approach. We recently demonstrated the utility of parallel multi-omics for the identification of T1D biomarker signatures. Our studies also identified challenges. Methods: Here, we evaluated a novel computational approach of data imputation and amplification as one way to overcome challenges associated with the relatively small number of subjects in these studies. Results: Using proprietary algorithms, we amplified our quadra-omics (proteomics, metabolomics, lipidomics, and transcriptomics) dataset from nine subjects a thousand-fold and analyzed the data using Ingenuity Pathway Analysis (IPA) software to assess the change in its analytical capabilities and biomarker prediction power in the amplified datasets compared to the original. These studies showed the ability to identify an increased number of T1D-relevant pathways and biomarkers in such computationally amplified datasets, especially, at imputation ratios close to the “golden ratio” of 38.2%:61.8%. Specifically, the Canonical Pathway and Diseases and Functions modules identified higher numbers of inflammatory pathways and functions relevant to autoimmune T1D, including novel ones not identified in the original data. The Biomarker Prediction module also predicted in the amplified data several unique biomarker candidates with direct links to T1D pathogenesis. Conclusions: These preliminary findings indicate that such large-scale data imputation and amplification approaches are useful in facilitating the discovery of candidate integrated biomarker signatures of T1D or other diseases by increasing the predictive range of existing data mining tools, especially when the size of the input data is inherently limited. 

In this work, we formulate and solve a new type of approximate nearest neighbor search (ANNS) problems called ANNS after linear transformation (ALT). In ANNS-ALT, we search for the vector (in a dataset) that, after being linearly transformed by a user-specified query matrix, is closest to a query vector. It is a very general mother problem in the sense that a wide range of baby ANNS problems that have important applications in databases and machine learning can be reduced to and solved as ANNS-ALT, or its dual that we call ANNS-ALTD. We propose a novel and computationally efficient solution, called ONe Index for All Kernels (ONIAK), to ANNS-ALT and all its baby problems when the data dimension d is not too large (say d ≤ 200). In ONIAK, a universal index is built, once and for all, for answering all future ANNS-ALT queries that can have distinct query matrices. We show by experiments that, when d is not too large, ONIAK has better query performance than linear scan on the mother problem (of ANNS-ALT), and has query performances comparable to those of the state-of-the-art solutions on the baby problems. However, the algorithmic technique behind this universal index approach suffers from a so-called dimension blowup problem that can make the indexing time prohibitively long for a large dataset. We propose a novel algorithmic technique, called fast GOE quadratic form (FGoeQF), that completely solves the (prohibitively long indexing time) fallout of the dimension blowup problem. We also propose a Johnson-Lindenstrauss transform (JLT) based ANNS-ALT (and ANNS-ALTD) solution that significantly outperforms any competitor when d is large. 

Multi-site clinical trial systems face security challenges when streamlining information sharing while protecting patient privacy. In addition, patient enrollment, transparency, traceability, data integrity, and reporting in clinical trial systems are all critical aspects of maintaining data compliance. A Blockchain-based clinical trial framework has been proposed by lots of researchers and industrial companies recently, but its limitations of lack of data governance, limited confidentiality, and high communication overhead made data-sharing systems insecure and not efficient. We propose 𝖲𝗈𝗍𝖾𝗋𝗂𝖺, a privacy-preserving smart contracts framework, to manage, share and analyze clinical trial data on fabric private chaincode (FPC). Compared to public Blockchain, fabric has fewer participants with an efficient consensus protocol. 𝖲𝗈𝗍𝖾𝗋𝗂𝖺 consists of several modules: patient consent and clinical trial approval management chaincode, secure execution for confidential data sharing, API Gateway, and decentralized data governance with adaptive threshold signature (ATS). We implemented two versions of 𝖲𝗈𝗍𝖾𝗋𝗂𝖺 with non-SGX deploys on AWS blockchain and SGX-based on a local data center. We evaluated the response time for all of the access endpoints on AWS Managed Blockchain, and demonstrated the utilization of SGX-based smart contracts for data sharing and analysis.