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Background: Type 1 diabetes (T1D) is a devastating autoimmune disease, and its rising prevalence in the United States and around the world presents a critical problem in public health. While some treatment options exist for patients already diagnosed, individuals considered at risk for developing T1D and who are still in the early stages of their disease pathogenesis without symptoms have no options for any preventive intervention. This is because of the uncertainty in determining their risk level and in predicting with high confidence who will progress, or not, to clinical diagnosis. Biomarkers that assess one’s risk with high certainty could address this problem and will inform decisions on early intervention, especially in children where the burden of justifying treatment is high. Single omics approaches (e.g., genomics, proteomics, metabolomics, etc.) have been applied to identify T1D biomarkers based on specific disturbances in association with the disease. However, reliable early biomarkers of T1D have remained elusive to date. To overcome this, we previously showed that parallel multi-omics provides a more comprehensive picture of the disease-associated disturbances and facilitates the identification of candidate T1D biomarkers. Methods: This paper evaluated the use of machine learning (ML) using data augmentation and supervised ML methods for the purpose of improving the identification of salient patterns in the data and the ultimate extraction of novel biomarker candidates in integrated parallel multi-omics datasets from a limited number of samples. We also examined different stages of data integration (early, intermediate, and late) to assess at which stage supervised parametric models can learn under conditions of high dimensionality and variation in feature counts across different omics. In the late integration scheme, we employed a multi-view ensemble comprising individual parametric models trained over single omics to address the computational challenges posed by the high dimensionality and variation in feature counts across the different yet integrated multi-omics datasets. Results: the multi-view ensemble improves the prediction of case vs. control and finds the most success in flagging a larger consistent set of associated features when compared with chance models, which may eventually be used downstream in identifying a novel composite biomarker signature of T1D risk. Conclusions: the current work demonstrates the utility of supervised ML in exploring integrated parallel multi-omics data in the ongoing quest for early T1D biomarkers, reinforcing the hope for identifying novel composite biomarker signatures of T1D risk via ML and ultimately informing early treatment decisions in the face of the escalating global incidence of this debilitating disease. 

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. 

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. 

Set reconciliation is a fundamental algorithmic problem that arises in many networking, system, and database applications. In this problem, two large sets A and B of objects (bitcoins, files, records, etc.) are stored respectively at two different network-connected hosts, which we name Alice and Bob respectively. Alice and Bob communicate with each other to learn A Δ B , the difference between A and B , and as a result the reconciled set A ∪ B. Current set reconciliation schemes are based on either invertible Bloom filters (IBF) or error-correction codes (ECC). The former has a low computational complexity of O(d) , where d is the cardinality of A Δ B , but has a high communication overhead that is several times larger than the theoretical minimum. The latter has a low communication overhead close to the theoretical minimum, but has a much higher computational complexity of O(d 2 ). In this work, we propose Parity Bitmap Sketch (PBS), an ECC-based set reconciliation scheme that gets the better of both worlds: PBS has both a low computational complexity of O(d) just like IBF-based solutions and a low communication overhead of roughly twice the theoretical minimum. A separate contribution of this work is a novel rigorous analytical framework that can be used for the precise calculation of various performance metrics and for the near-optimal parameter tuning of PBS.