Characteristic Functions on Graphs: Birds of a Feather, from Statistical Descriptors to Parametric Models

In this paper, we propose a flexible notion of characteristic functions defined on graph vertices to describe the distribution of vertex features at multiple scales. We introduce FEATHER, a computationally efficient algorithm to calculate a specific variant of these characteristic functions where the probability weights of the characteristic function are defined as the transition probabilities of random walks. We argue that features extracted by this procedure are useful for node level machine learning tasks. We discuss the pooling of these node representations, resulting in compact descriptors of graphs that can serve as features for graph classification algorithms. We analytically prove that FEATHER describes isomorphic graphs with the same representation and exhibits robustness to data corruption. Using the node feature characteristic functions we define parametric models where evaluation points of the functions are learned parameters of supervised classifiers. Experiments on real world large datasets show that our proposed algorithm creates high quality representations, performs transfer learning efficiently, exhibits robustness to hyperparameter changes, and scales linearly with the input size.Comment: Source code is available at: https://github.com/benedekrozemberczki/FEATHE

Anatomical patterns of recurrence following biochemical relapse after post‐prostatectomy salvage radiation therapy: a multi‐institutional study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138303/1/bju13792.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138303/2/bju13792_am.pd

Disparities in preventive procedures: comparisons of self-report and Medicare claims data

BACKGROUND: Racial/ethnic disparities are assessed using either self-report or claims data. We compared these two data sources and examined contributors to discrepancies in estimates of disparities. METHODS: We analyzed self-report and matching claims data from Medicare Beneficiaries 65 and older who participated in the Medicare Current Beneficiary Survey, 1999–2002. Six preventive procedures were included: PSA testing, influenza vaccination, Pap smear testing, cholesterol testing, mammography, and colorectal cancer testing. We examined predictors of self-reports in the absence of claims and claims in the absence of self-reports. RESULTS: With the exception of PSA testing, racial/ethnic disparities in preventive procedures are generally larger when using Medicare claims than when using patients' self-report. Analyses adjusting for age, gender, income, educational level, health status, proxy response and supplemental insurance showed that minorities were more likely to self-report preventive procedures in the absence of claims. Adjusted odds ratios ranged from 1.07 (95% CI: 0.88 – 1.30) for PSA testing to 1.83 (95% CI: 1.46 – 2.30) for Pap smear testing. Rates of claims in the absence of self-report were low. Minorities were more likely to have PSA test claims in the absence of self-reports (1.55 95% CI: 1.17 – 2.06), but were less likely to have influenza vaccination claims in the absence of self-reports (0.69 95% CI: 0.51 – 0.93). CONCLUSION: These findings are consistent with either racial/ethnic reporting biases in receipt of preventive procedures or less efficient Medicare billing among providers with large minority practices

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10−14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10−4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10−8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10−9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10−7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS–SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved