ALID: Scalable Dominant Cluster Detection

Detecting dominant clusters is important in many analytic applications. The state-of-the-art methods find dense subgraphs on the affinity graph as the dominant clusters. However, the time and space complexity of those methods are dominated by the construction of the affinity graph, which is quadratic with respect to the number of data points, and thus impractical on large data sets. To tackle the challenge, in this paper, we apply Evolutionary Game Theory (EGT) and develop a scalable algorithm, Approximate Localized Infection Immunization Dynamics (ALID). The major idea is to perform Localized Infection Immunization Dynamics (LID) to find dense subgraph within local range of the affinity graph. LID is further scaled up with guaranteed high efficiency and detection quality by an estimated Region of Interest (ROI) and a carefully designed Candidate Infective Vertex Search method (CIVS). ALID only constructs small local affinity graphs and has a time complexity of O(C(a^*+ {\delta})n) and a space complexity of O(a^*(a^*+ {\delta})), where a^* is the size of the largest dominant cluster and C << n and {\delta} << n are small constants. We demonstrate by extensive experiments on both synthetic data and real world data that ALID achieves state-of-the-art detection quality with much lower time and space cost on single machine. We also demonstrate the encouraging parallelization performance of ALID by implementing the Parallel ALID (PALID) on Apache Spark. PALID processes 50 million SIFT data points in 2.29 hours, achieving a speedup ratio of 7.51 with 8 executors

Analysis of the putative role of CR1 in Alzheimer’s disease: Genetic association, expression and function

Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved

Heteroplasmy and Individual Mitogene Pools: Characteristics and Potential Roles in Ecological Studies

The mitochondrial genome (mitogenome or mtDNA), the extrachromosomal genome, is a multicopy circular DNA with high mutation rates due to replication and repair errors. A mitochondrion, cell, tissue, organ, or an individual body may hold multiple variants, both inherited and developed over a lifetime, which make up individual mitogene pools. This phenomenon is also called mtDNA heteroplasmy. MtDNA variants influence cellular and tissular functions and are consequently subjected to selection. Although it has long been recognized that only inheritable germline heteroplasmies have evolutionary significance, non-inheritable somatic heteroplasmies have been overlooked since they directly affect individual fitness and thus indirectly affect the fate of heritable germline variants. This review focuses on the characteristics, dynamics, and functions of mtDNA heteroplasmy and proposes the concept of individual mitogene pools to discuss individual genetic diversity from multiple angles. We provide a unique perspective on the relationship between individual genetic diversity and heritable genetic diversity and guide how the individual mitogene pool with novel genetic markers can be applied to ecological research

Correlation Analysis between GDM and Gut Microbial Composition in Late Pregnancy

The prevalence of GDM is very high worldwide. The specific pathogenesis of GDM is currently not very clear. Recent research suggests that changes in the intestinal flora during pregnancy play a key role in it. Therefore, this study is aimed at exploring the characteristics of the intestinal flora of patients with gestational diabetes in the third trimester of pregnancy and at finding the intestinal flora with significant differences in healthy pregnant women to provide a basis for future clinical attempts of using intestinal microecological agents to treat gestational diabetes mellitus (GDM). We sequenced the V3-V4 regions of the 16S ribosomal ribonucleic acid (rRNA) gene from stool samples of 52 singleton pregnant women at >28 weeks of gestation. Our results showed that there were significant differences between the NOR group vs. GDM group and the G group vs. LG group among Bacteroides, Firmicutes, and Firmicutes/Bacteroides. At the species level, there were significant differences in the abundance of eight species in the NOR and GDM groups. Among them, the relative abundance of Clostridium_spiroforme, Eubacterium_dolichum, and Ruminococcus_gnavus was positively correlated with FBG, and Pyramidobacter_piscolens was negatively correlated with FBG, whereas there were significant differences in the abundance of five species in the G and LG groups. Functional analysis showed that there were differences in the biosynthesis and metabolism of polysaccharides, digestive system, classification, and degradation of the intestinal microbes between the NOR and GDM groups and between the G and LG groups. These results indicated that the gut microbes between GDM patients in the third trimester of pregnancy and healthy controls had essential characteristic changes and might be involved in the regulation of patients’ blood glucose levels

Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells

Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells (iPSCs) from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation (c.3226C>T, p.R1076C). Vascular smooth muscle cells (VSMCs) differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes, including activation of the NOTCH and NF-κB signaling pathway, cytoskeleton disorganization, and excessive cell proliferation. In comparison, these abnormalities were not observed in vascular endothelial cells (VECs) derived from the patient’s iPSCs. Importantly, the abnormal upregulation of NF-κB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor, providing a potential therapeutic strategy for CADASIL. Overall, using this iPSC-based disease model, our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease