Finding Distance-Preserving Subgraphs in Large Road Networks

Abstract-Given two sets of points, S and T , in a road network, G, a distance-preserving subgraph (DPS) query returns a subgraph of G that preserves the shortest path from any point in S to any point in T . DPS queries are important in many real world applications, such as route recommendation systems, logistics planning, and all kinds of shortest-path-related applications that run on resource-limited mobile devices. In this paper, we study efficient algorithms for processing DPS queries in large road networks. Four algorithms are proposed with different tradeoffs in terms of DPS quality and query processing time, and the best one is a graph-partitioning based index, called RoadPart, that finds a high quality DPS with short response time. Extensive experiments on large road networks demonstrate the merits of our algorithms, and verify the efficiency of RoadPart for finding a high-quality DPS

Long Span DNA Paired-End-Tag (DNA-PET) Sequencing Strategy for the Interrogation of Genomic Structural Mutations and Fusion-Point-Guided Reconstruction of Amplicons

10.1371/journal.pone.0046152PLoS ONE79

Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity.

Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed. Cell Rep 2015 Jul 14; 12(2):272-285

Joint sensing duty cycle scheduling for heterogeneous coverage guarantee

In this paper we study the following problem: given a set of m sensors that collectively cover a set of n target points with heterogeneous coverage requirements (target j needs to be covered every fj slots), how to schedule the sensor duty cycles such that all coverage requirements are satisfied and the maximum number of sensors turned on at any time slot is minimized. The problem models varied real-world applications in which sensing tasks exhibit high discrepancy in coverage requirements - critical locations often need to be covered much more frequently. We provide multiple algorithms with best approximation ratio of O (log n + log m) for the maximum number of sensors to turn on, and bi-criteria algorithm with (α, β)-approximation factors with high probability, where the number of sensors turned on is an α = O(δ(log (n) + log(m))/β)-approximation of the optimal (satisfying all requirements) and the coverage requirement is a β-approximation; δ is the approximation ratio achievable in an appropriate instance of set multi-cover. When the sensor coverage exhibits extra geometric properties, the approximation ratios can be further improved. We also evaluated our algorithms via simulations and experiments on a camera testbed. The performance improvement (energy saving) is substantial compared to turning on all sensors all the time, or a random scheduling baseline

Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes

Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA–PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers

Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape

Abstract Objective To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. Methods This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. Results A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81–1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. Conclusion This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry