Funded Competitive Renewal Project Title: Transfer Rule Learning with Functional Mapping for Integrative Modeling of Panomics Data
The major goal of this project is develop, apply, and evaluate novel Transfer Rule Learning (TRL) methods for integrative biomarker discovery from related biomedical data sets.
Wagner M, Tsui F, Cooper G, Espino JU, Harkema H, Levander J, Villamarin R, Voorhees R, Millett N, Keane C, Dey A, Razdan M, Hu Y, Tsai M, Brown S, Lee BY, Gallagher A, Potter M. Probabilistic, Decision-theoretic Disease Surveillance and Control. Online J Public Health Inform. 2011;3(3) doi: 10.5210/ojphi.v3i3.3798. Epub 2011 Dec 22. PubMed PMID: 23569617. PMCID: PMC3615794.
The Pittsburgh Center of Excellence in Public Health Informatics has developed a probabilistic, decision-theoretic system for disease surveillance and control for use in Allegheny County, PA and later in Tarrant County, TX. This paper describes the software components of the system and its knowledge bases. The paper uses influenza surveillance to illustrate how the software components transform data collected by the healthcare system into population level analyses and decision analyses of potential outbreak-control measures.
Proteomic analysis of stage I endometrial cancer tissue: identification of proteins associated with oxidative processes and inflammation.
Maxwell GL, Hood BL, Day R, Chandran U, Kirchner D, Kolli VS, Bateman NW, Allard J, Miller C, Sun M, Flint MS, Zahn C, Oliver J, Banerjee S, Litzi T, Parwani A, Sandburg G, Rose S, Becich MJ, Berchuck A, Kohn E, Risinger JI, Conrads TP.Proteomic analysis of stage I endometrial cancer tissue: Identification of proteins associated with oxidative processes and inflammation.Gynecol Oncol. 2011 Jun 1;121(3):586-94. Epub 2011 Apr 1. PMID: 21458040 PubMed Journal - in process
The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection.
A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins.
209 differentially expressed proteins were identified in a comparison of stage I endometrial cancers and normal post-menopausal endometrium controls (Q<0.005). A number of differentially abundant proteins in stage I endometrial cancer were identified and independently validated by western blot and tissue microarray analyses. Multiple proteins identified with elevated abundance in stage I endometrial cancer are functionally associated with inflammation (annexins) and oxidative processes (peroxiredoxins). PRDX1 and ANXA2 were both confirmed as being overexpressed in stage I cancer compared to normal endometrium by independent TMA (Q=0.008 and Q=0.00002 respectively).
These data provide the basis for further investigation of previously unrecognized novel pathways involved in early stage endometrial carcinogenesis and provide possible targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.
Published by Elsevier Inc.
Immunohistochemical Analysis of ezrin-radixin-moesin-binding phosphoprotein 50 in prostatic adenocarcinoma
Batholow TL, Becich MJ, Chandran UR, Parwani AV. Immunohistochemical Analysis of ezrin-radixin-moesin-binding phosphoprotein 50 in prostatic adenocarcinoma. BMC Urol. 2011 Jun 14;11(1):12. [Epub ahead of print] PMID: 21672215. PMC 3132203
Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis. Here we use immunohistochemistry to evaluate EBP50's expression in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).
Tissue microarrays were immunohistochemically stained for EBP50, with the staining intensities quantified using automated image analysis software. The data were statistically analyzed using one-way ANOVA with subsequent Tukey tests for multiple comparisons. Eleven cases of NDP, 37 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 103 cases of PCa, and 36 cases of Mets were analyzed in the microarrays.
Specimens of PCa and Mets had the lowest absolute staining for EBP50. Mets staining was significantly lower than NDP (p = 0.027), BPH (p = 0.012), NAC (p < 0.001), HGPIN (p < 0.001), and PCa (p = 0.006). Additionally, HGPIN staining was significantly higher than NAC (p < 0.009) and PCa (p < 0.001).
To our knowledge, this represents the first study comparing the immunohistochemical profiles of EBP50 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC and suggests that EBP50 expression is decreased in Mets. Given that PCa also had significantly higher expression than Mets, future studies are warranted to assess EBP50's potential as a prognostic biomarker for prostate cancer.
Bartholow TL, Becich MJ, Chandran UR, Parwani AV. Immunohistochemical staining of slit2 in primary and metastatic prostatic adenocarcinoma. Transl Oncol. 2011 Oct;4(5):314-20. Epub 2011 Oct 1. PMC 3162306
BACKGROUND: Conflicting roles for Slit2, a protein involved in mediating the processes of cell migration and chemotactic response, have been previously described in prostate cancer. Here we use immunohistochemistry to evaluate the expression of Slit2 in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets). METHODS: Tissue microarrays were immunostained for Slit2. The staining intensities were quantified using automated image analysis software. The data was statistically analyzed using one-way analysis of variance with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Eleven cases of NDP, 35 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 106 cases of PCa, and 37 cases of Mets were analyzed. RESULTS: Specimens of PCa and HGPIN had the highest absolute staining for Slit2. Significant differences were seen between PCa and NDP (P < .05), PCa and NAC (P < .05), HGPIN and NDP (P < .05), and HGPIN and NAC (P < .05). Whereas the average Mets staining was not significantly different from NDP or NAC, several individual Mets cases featured intense staining. CONCLUSIONS: To our knowledge, this represents the first study comparing the immunohistochemical profiles of Slit2 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC. These findings suggest that Slit2 expression can be increased in HGPIN, PCa, and Mets, making it a potentially important biomarker for prostate cancer.
Senior Research Specialist
Assessing the Usability of a Telemedicine-based Medication Delivery Unit for Older Adults through Inspection Methods
Ligons FM, Romagnoli KM, Browell S, Hochheiser H, Handler SM. Assessing the Usability of a Telemedicine-based Medication Delivery Unit for Older Adults through Inspection Methods. AMIA 2011. 2011.
Polypharmacy and medication non-adherence are common in older adults, potentially leading to medication-related problems and increased healthcare expenditures. Medication Delivery Units (MDUs) may improve adherence, but their interfaces may present usability challenges for older adults with age-related impairments. We used a combination of three inspection methods - heuristic evaluation, cognitive walkthrough, and simulated elderly interaction, to identify potential concerns with the usability of a commercially available telemedicine MDU. Each method revealed different problems, with repeated discoveries via different methods providing triangulated evidence. Despite the MDU's general usability, issues of varying severity were discovered. Significant usability issues associated with physical interactions with the MDU included loading and unloading the medication blister packs, and opening the delivered medication prior to administration. Less severe issues centered on small text sizes and poor user feedback. Further usability testing, involving older adults with a variety of impairments, is needed to validate findings.