Informatics Metrics and Measures for a Smart Public Health Systems Approach: Information Science Perspective

Public health informatics is an evolving domain in which practices constantly change to meet the demands of a highly complex public health and healthcare delivery system. Given the emergence of various concepts, such as learning health systems, smart health systems, and adaptive complex health systems, health informatics professionals would benefit from a common set of measures and capabilities to inform our modeling, measuring, and managing of health system “smartness.” Here, we introduce the concepts of organizational complexity, problem/issue complexity, and situational awareness as three codependent drivers of smart public health systems characteristics. We also propose seven smart public health systems measures and capabilities that are important in a public health informatics professional’s toolkit

An Organizational Informatics Analysis of Colorectal, Breast, and Cervical Cancer Screening Clinical Decision Support and Information Systems within Community Health Centers

Indiana University-Purdue University Indianapolis (IUPUI)A study design has been developed that employs a dual modeling approach to identify factors associated with facility-level cancer screening improvement and how this is mediated by the use of clinical decision support. This dual modeling approach combines principles of (1) Health Informatics, (2) Cancer Prevention and Control, (3) Health Services Research, and (4) Organizational Change/Theory. The study design builds upon the constructs of a conceptual framework developed by Jane Zapka, namely, (1) organizational and/or practice settings, (2) provider characteristics, and (3) patient population characteristics. These constructs have been operationalized as measures in a 2005 HRSA/NCI Health Disparities Cancer Collaborative inventory of 44 community health centers. The first, statistical models will use: sequential, multivariable regression models to test for the organizational determinants that may account for the presence and intensity-of-use of clinical decision support (CDS) and information systems (IS) within community health centers for use in colorectal, breast, and cervical cancer screening. A subsequent test will assess the impact of CDS/IS on provider reported cancer screening improvement rates. The second, computational models will use a multi-agent model of network evolution called CONSTRUCT® to identify the agents, tasks, knowledge, groups, and beliefs associated with cancer screening practices and CDS/IS use to inform both CDS/IS implementation and cancer screening intervention strategies. This virtual experiment will facilitate hypothesis-generation through computer simulation exercises. The outcome of this research will be to identify barriers and facilitators to improving community health center facility-level cancer screening performance using CDS/IS as an agent of change. Stakeholders for this work include both national and local community health center IT leadership, as well as clinical managers deploying IT strategies to improve cancer screening among vulnerable patient populations

Hypothesis Generation Using Network Structures on Community Health Center Cancer-Screening Performance

RESEARCH OBJECTIVES: Nationally sponsored cancer-care quality-improvement efforts have been deployed in community health centers to increase breast, cervical, and colorectal cancer-screening rates among vulnerable populations. Despite several immediate and short-term gains, screening rates remain below national benchmark objectives. Overall improvement has been both difficult to sustain over time in some organizational settings and/or challenging to diffuse to other settings as repeatable best practices. Reasons for this include facility-level changes, which typically occur in dynamic organizational environments that are complex, adaptive, and unpredictable. This study seeks to understand the factors that shape community health center facility-level cancer-screening performance over time. This study applies a computational-modeling approach, combining principles of health-services research, health informatics, network theory, and systems science. METHODS: To investigate the roles of knowledge acquisition, retention, and sharing within the setting of the community health center and to examine their effects on the relationship between clinical decision support capabilities and improvement in cancer-screening rate improvement, we employed Construct-TM to create simulated community health centers using previously collected point-in-time survey data. Construct-TM is a multi-agent model of network evolution. Because social, knowledge, and belief networks co-evolve, groups and organizations are treated as complex systems to capture the variability of human and organizational factors. In Construct-TM, individuals and groups interact by communicating, learning, and making decisions in a continuous cycle. Data from the survey was used to differentiate high-performing simulated community health centers from low-performing ones based on computer-based decision support usage and self-reported cancer-screening improvement. RESULTS: This virtual experiment revealed that patterns of overall network symmetry, agent cohesion, and connectedness varied by community health center performance level. Visual assessment of both the agent-to-agent knowledge sharing network and agent-to-resource knowledge use network diagrams demonstrated that community health centers labeled as high performers typically showed higher levels of collaboration and cohesiveness among agent classes, faster knowledge-absorption rates, and fewer agents that were unconnected to key knowledge resources. Conclusions and research implications: Using the point-in-time survey data outlining community health center cancer-screening practices, our computational model successfully distinguished between high and low performers. Results indicated that high-performance environments displayed distinctive network characteristics in patterns of interaction among agents, as well as in the access and utilization of key knowledge resources. Our study demonstrated how non-network-specific data obtained from a point-in-time survey can be employed to forecast community health center performance over time, thereby enhancing the sustainability of long-term strategic-improvement efforts. Our results revealed a strategic profile for community health center cancer-screening improvement via simulation over a projected 10-year period. The use of computational modeling allows additional inferential knowledge to be drawn from existing data when examining organizational performance in increasingly complex environments

Using computational modeling to assess the impact of clinical decision support on cancer screening improvement strategies within the community health centers

AbstractOur conceptual model demonstrates our goal to investigate the impact of clinical decision support (CDS) utilization on cancer screening improvement strategies in the community health care (CHC) setting. We employed a dual modeling technique using both statistical and computational modeling to evaluate impact. Our statistical model used the Spearman’s Rho test to evaluate the strength of relationship between our proximal outcome measures (CDS utilization) against our distal outcome measure (provider self-reported cancer screening improvement). Our computational model relied on network evolution theory and made use of a tool called Construct-TM to model the use of CDS measured by the rate of organizational learning. We employed the use of previously collected survey data from community health centers Cancer Health Disparities Collaborative (HDCC). Our intent is to demonstrate the added valued gained by using a computational modeling tool in conjunction with a statistical analysis when evaluating the impact a health information technology, in the form of CDS, on health care quality process outcomes such as facility-level screening improvement. Significant simulated disparities in organizational learning over time were observed between community health centers beginning the simulation with high and low clinical decision support capability

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

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

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

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

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies