The PathOlogist: an automated tool for pathway-centric analysis

<p>Abstract</p> <p>Background</p> <p>The PathOlogist is a new tool designed to transform large sets of gene expression data into quantitative descriptors of pathway-level behavior. The tool aims to provide a robust alternative to the search for single-gene-to-phenotype associations by accounting for the complexity of molecular interactions.</p> <p>Results</p> <p>Molecular abundance data is used to calculate two metrics - 'activity' and 'consistency' - for each pathway in a set of more than 500 canonical molecular pathways (source: Pathway Interaction Database, <url>http://pid.nci.nih.gov</url>). The tool then allows a detailed exploration of these metrics through integrated visualization of pathway components and structure, hierarchical clustering of pathways and samples, and statistical analyses designed to detect associations between pathway behavior and clinical features.</p> <p>Conclusions</p> <p>The PathOlogist provides a straightforward means to identify the functional processes, rather than individual molecules, that are altered in disease. The statistical power and biologic significance of this approach are made easily accessible to laboratory researchers and informatics analysts alike. Here we show as an example, how the PathOlogist can be used to establish pathway signatures that robustly differentiate breast cancer cell lines based on response to treatment.</p

J Acquir Immune Defic Syndr

BackgroundCervical cancer is a major public health problem in resource-limited settings, particularly among HIV-infected women. Given the challenges of cytology-based approaches, the efficiency of new screening programs need to be assessed.SettingCommunity and hospital-based clinics in Gaborone, Botswana.ObjectiveTo determine the feasibility, and efficiency of the \u201cSee and Treat\u201d approach using Visual Inspection Acetic Acid (VIA) and Enhanced Digital Imaging (EDI) for cervical cancer prevention in HIV-infected women.MethodsA two-tier community-based cervical cancer prevention program was implemented. HIV-infected women were screened by nurses at the community using the VIA/EDI approach. Low-grade lesions were treated with cryotherapy on the same visit.ResultsFrom March 2009 through January 2011, 2,175 patients were screened for cervical cancer at our community-based clinic. 253 (11.6%) were found to have low-grade lesions and received same-day cryotherapy. 1,347 (61.9%) women were considered to have a normal examination and 575 (27.3%) were referred for further evaluation and treatment. Of the 1,347 women initially considered to have normal exams, 267 (19.8%) were recalled based on weekly quality control assessments. 210 (78.6%) of the 267 recalled women and 499 (86.8%) of the 575 referred women were seen at the referral clinic. Of these 709 women, 506 (71.4%) required additional treatment. Overall, 264 CIN stage 2 or 3 were identified and treated, and six micro-invasive cancers identified were referred for further management.ConclusionsOur \u201cSee and Treat\u201d cervical cancer prevention program using the VIA/EDI approach is a feasible, high-output and high-efficiency program, worthy of considering as an additional cervical cancer screening method in Botswana, especially for women with limited access to the current cytology-based screening services.20122014-01-08T00:00:00ZP30 AI045008/AI/NIAID NIH HHS/United StatesU2G PS001949/PS/NCHHSTP CDC HHS/United States1U2GPS001949/PHS HHS/United StatesIP30 AI 45008/AI/NIAID NIH HHS/United States22134146PMC388408