Wireless power and communication system for medical implants

This thesis aims to examine the hypothesis that “Power of more than 1 mW can be received by the microsystem inside a human body through a wireless magnetic coupling link with a receiver of a diameter less than 2mm from a transfer distance as much as 20 cm” and “Data can be transmitted wirelessly from the microsystem to an external reader using the same magnetic coupling link as the wireless power system”. A 3-coil weakly coupled magnetic resonance wireless power transfer system has been built based on solenoid coils. The design of the transmitter of the system includes the designs of a single-turn coupling coil and a multi-turn primary coil. To maximise the magnetic field generated by the transmitter, the relative position of the two coils is optimised to match the impedances of the coils. Design flow is reported for the optimum dimensional parameters (coil diameter, gap interval, number of turns) of the primary coil after a detailed analysis of the co-dependencies of the parameters. The design of the receiver of the system includes the designs of the receiver coil and the rectifier. Two kinds of solenoid receiver coils have been analysed, the air-core coil and the ferrite-core coil. Due to the size limitation (2 mm-diameter) of the receiver, only the ferrite-core solenoid coil is able to meet the power demand. Design flow of the ferrite-core coil is reported. In terms of the rectifier, a novel static gate-control bootstrapping rectifier (static BSR) and a novel opto-coupled dynamic gate-control (OCDGC) bootstrapping rectifier are reported, which have low power consumption and high power conversion efficiency compared with junction-diode rectifiers and comparator-based rectifiers. The power delivered to load (PDL) of the whole WPT system is tested in air and human conductive tissue at transfer distances within 20 cm with consideration of rectifier power conversion efficiencies and different load conditions (500 Ω and 5 kΩ). Results show that, at 20 cm transfer distance, the system will be able to meet the 1 mW power demand for light load condition (5 kΩ) both in air and in human conductive tissue; But in heavy load condition (500 Ω), a high number of receiver coil turns will be needed to meet the power demand. The sensitivity of the data transfer of the whole WPT system is also analysed based on load shift keying (LSK) modulation. The S-parameter S11 ratio is the Figure of Merit (FOM) of the data transfer analysis. It can be concluded that the hypotheses of the thesis are feasible, which is an inspiration of multiple deep-tissue micro-implants for medical purposes

CAFuncAPA: A Knowledgebase for Systematic Functional Annotations of APA Events in Human Cancers

Alternative polyadenylation (APA) is a widespread posttranscriptional regulation process. APA generates diverse mRNA isoforms with different 3\u27 UTR lengths, affecting mRNA expression, miRNA binding regulation and alternative splicing events. Previous studies have demonstrated the important roles of APA in tumorigenesis and cancer progression through diverse aspects. Thus, a comprehensive functional landscape of diverse APA events would aid in a better understanding of the underlying mechanisms related to APA in human cancers. Here, we built CAFuncAPA (https://relab.xidian.edu.cn/CAFuncAPA/) to systematically annotate the functions of 15478 APA events in human pan-cancers. Specifically, we first identified APA events associated with cancer survival and tumor progression. We annotated the potential downstream effects of APA on genes/isoforms expression, regulation of miRNAs, RNA binding proteins (RBPs) and alternative splicing events. Moreover, we also identified up-regulators of APA events, including the effects of genetic variants on poly(A) sites and RBPs, as well as the effect of methylation phenotypes on APA events. These findings suggested that CAFuncAPA can be a helpful resource for a better understanding of APA regulators and potential functions in cancer biology

The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases in APOL1, IGFBP3, GRIA2, BLCAP, and miR-589-3p. These events might play crucial roles in the scenarios of tumorigenesis, due to their tumor-related editing frequencies or probable effects on altered expression profiles, protein functions, splicing patterns, and microRNA regulations of tumor genes. Our functional A-to-I RNA editing events (https://ccsm.uth.edu/CAeditome/) will help better understand the cancer pathology from the A-to-I RNA editing aspect

Inferring Evolutionary Trajectories From Cross-Sectional Transcriptomic Data to Mirror Lung Adenocarcinoma Progression

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased

scProAtlas: An Atlas of Multiplexed Single-Cell Spatial Proteomics Imaging in Human Tissues

Spatial proteomics can visualize and quantify protein expression profiles within tissues at single-cell resolution. Although spatial proteomics can only detect a limited number of proteins compared to spatial transcriptomics, it provides comprehensive spatial information with single-cell resolution. By studying the spatial distribution of cells, we can clearly obtain the spatial context within tissues at multiple scales. Spatial context includes the spatial composition of cell types, the distribution of functional structures, and the spatial communication between functional regions, all of which are crucial for the patterns of cellular distribution. Here, we constructed a comprehensive spatial proteomics functional annotation knowledgebase, scProAtlas (https://relab.xidian.edu.cn/scProAtlas/#/), which is designed to help users comprehensively understand the spatial context within different tissue types at single-cell resolution and across multiple scales. scProAtlas contains multiple modules, including neighborhood analysis, proximity analysis and neighborhood network, to comprehensively construct spatial cell maps of tissues and multi-modal integration, spatial gene identification, cell-cell interaction and spatial pathway analysis to display spatial variable genes. scProAtlas includes data from eight spatial protein imaging techniques across 15 tissues and provides detailed functional annotation information for 17 468 394 cells from 945 region of interests. The aim of scProAtlas is to offer a new insight into the spatial structure of various tissues and provides detailed spatial functional annotation

Genetic Control of RNA Editing in Neurodegenerative Disease

A-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variants. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership-Alzheimer\u27s Disease and Parkinson\u27s Progression Markers Initiative. The large-scale and genome-wide identification of 95 198 RNA editing quantitative trait loci revealed the preferred genetic effects on adjacent editing events. Furthermore, to explore the underlying mechanisms of the genetic controls of A-to-I RNA editing, several top RNA-binding proteins were pointed out, such as EIF4A3, U2AF2, NOP58, FBL, NOP56 and DHX9, since their regulations on multiple RNA-editing events were probably interfered by these genetic variants. Moreover, these variants may also contribute to the variability of other molecular phenotypes associated with RNA editing, including the functions of 3 proteins, expressions of 277 genes and splicing of 449 events. All the analyses results shown in NeuroEdQTL (https://relab.xidian.edu.cn/NeuroEdQTL/) constituted a unique resource for the understanding of neurodegenerative pathogenesis from genotypes to phenotypes related to A-to-I RNA editing

AgeAnno: A Knowledgebase of Single-Cell Annotation of Aging in Human

Aging is a complex process that accompanied by molecular and cellular alterations. The identification of tissue-/cell type-specific biomarkers of aging and elucidation of the detailed biological mechanisms of aging-related genes at the single-cell level can help to understand the heterogeneous aging process and design targeted anti-aging therapeutics. Here, we built AgeAnno (https://relab.xidian.edu.cn/AgeAnno/#/), a knowledgebase of single cell annotation of aging in human, aiming to provide comprehensive characterizations for aging-related genes across diverse tissue-cell types in human by using single-cell RNA and ATAC sequencing data (scRNA and scATAC). The current version of AgeAnno houses 1 678 610 cells from 28 healthy tissue samples with ages ranging from 0 to 110 years. We collected 5580 aging-related genes from previous resources and performed dynamic functional annotations of the cellular context. For the scRNA data, we performed analyses include differential gene expression, gene variation coefficient, cell communication network, transcription factor (TF) regulatory network, and immune cell proportionc. AgeAnno also provides differential chromatin accessibility analysis, motif/TF enrichment and footprint analysis, and co-accessibility peak analysis for scATAC data. AgeAnno will be a unique resource to systematically characterize aging-related genes across diverse tissue-cell types in human, and it could facilitate antiaging and aging-related disease research

The Potential Regulation of A-to-I RNA Editing on Genes in Parkinson\u27s Disease.

Parkinson\u27s disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD\u27s transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis