ItemA Bayesian Latent Variable Approach to Aggregation of Partial and Top-Ranked Lists in Genomic Studies(Wiley) Li, X.; Choudhary, Pankaj K.; Biswas, Swati; Wang, X.; 0000 0001 2704 188X (Biswas, S); 0000-0002-0398-7459 (Choudary, PK); Choudhary, Pankaj K.; Biswas, SwatiIn genomic research, it is becoming increasingly popular to perform meta-analysis, the practice of combining results from multiple studies that target a common essential biological problem. Rank aggregation, a robust meta-analytic approach, consolidates such studies at the rank level. There exists extensive research on this topic, and various methods have been developed in the past. However, these methods have two major limitations when they are applied in the genomic context. First, they are mainly designed to work with full lists, whereas partial and/or top-ranked lists prevail in genomic studies. Second, the component studies are often clustered, and the existing methods fail to utilize such information. To address the above concerns, a Bayesian latent variable approach, called BiG, is proposed to formally deal with partial and top-ranked lists and incorporate the effect of clustering. Various reasonable prior specifications for variance parameters in hierarchical models are carefully studied and compared. Simulation results demonstrate the superior performance of BiG compared with other popular rank aggregation methods under various practical settings. A non–small-cell lung cancer data example is analyzed for illustration. ItemRecent Enhancements to the Genetic Risk Prediction Model BRCAPRO(Libertas Academica, 2015-05-10) Mazzola, Emanuele; Blackford, Amanda; Parmigiani, Giovanni; Biswas, Swati; 0000 0001 2704 188X (Biswas, S)BRCAPRO is a widely used model for genetic risk prediction of breast cancer. It is a function within the R package BayesMendel and is used to calculate the probabilities of being a carrier of a deleterious mutation in one or both of the BRCA genes, as well as the probability of being affected with breast and ovarian cancer within a defined time window. Both predictions are based on information contained in the counselee's family history of cancer. During the last decade, BRCAPRO has undergone several rounds of successive refinements: the current version is part of release 2.1 of BayesMendel. In this review, we showcase some of the most notable features of the software resulting from these recent changes. We provide examples highlighting each feature, using artificial pedigrees motivated by complex clinical examples. We illustrate how BRCAPRO is a comprehensive software for genetic risk prediction with many useful features that allow users the flexibility to incorporate varying amounts of available information.; ItemAn Improved Version of Logistic Bayesian Lasso for Detecting Rare Haplotype-Environment Interactions with Application to Lung Cancer(Libertas Academica, 2015-02-09) Zhang, Yuan; Biswas, Swati; 0000 0001 2704 188X (Biswas, S)The importance of haplotype association and gene-environment interactions (GxE) in the context of rare variants has been underlined in voluminous literature. Recently, a software based on logistic Bayesian LASSO (LBL) was proposed for detecting GxE, where G is a rare (or common) haplotype variant (rHTV)-it is called LBL-GxE. However, it required relatively long computation time and could handle only one environmental covariate with two levels. Here we propose an improved version of LBL-GxE, which is not only computationally faster but can also handle multiple covariates, each with multiple levels. We also discuss details of the software, including input, output, and some options. We apply LBL-GxE to a lung cancer dataset and find a rare haplotype with protective effect for current smokers. Our results indicate that LBL-GxE, especially with the improvements proposed here, is a useful and computationally viable tool for investigating rare haplotype interactions.; ItemImpact of a Community Based Implementation of Reach II Program for Caregivers of Alzheimer's Patients(PLOS, 2014-02-27) Lykens, Kristine; Moayad, Neda; Biswas, Swati; Reyes-Ortiz, Carlos; Singh, Karan P.; 0000 0001 2704 188X (Biswas, S)Background: In 2009 an estimated 5.3 million people in the United States were afflicted with Alzheimer's disease, a degenerative form of dementia. The impact of this disease is not limited to the patient but also has significant impact on the lives and health of their family caregivers. The Resources for Enhancing Alzheimer's Caregiver Health (REACH II) program was developed and tested in clinical studies. The REACH II program is now being delivered by community agencies in several locations. This study examines the impact of the REACH II program on caregiver lives and health in a city in north Texas. Study design: Family caregivers of Alzheimer's patients were assessed using an instrument covering the multi-item domains of Caregiver Burden, Depression, Self-Care, and Social Support upon enrollment in the program and at the completion of the 6 month intervention. The domain scores were analyzed using a multivariate paired t-test and Bonferroni confidence interval for the differences in pre- and post-service domain scores. Results: A total of 494 families were enrolled in the program during the period January 1, 2011 through June 30, 2012. Of these families 177 completed the 6 month program and have pre - and post service domain scores. The median age for the caregivers was 62 years. The domain scores for Depression and Caregiver Burden demonstrated statistically significant improvements upon program completion. Conclusion: The REACH II intervention was successfully implemented by a community agency with comparable impacts to those of the clinical trial warranting wider scale implementation. ItemReciprocal Regulation of Annexin A2 and EGFR with Her-2 in Her-2 Negative and Herceptin-Resistant Breast Cancer(PLOS, 2012-09-05) Shetty, Praveenkumar K.; Thamake, Sanjay I.; Biswas, Swati; Johansson, Sonny L.; Vishwanatha, Jamboor K.; 0000 0001 2704 188X (Biswas, S)Alternative survival pathways are commonly seen to be upregulated upon inhibition of receptor tyrosine kinases (RTK), including Her-2. It is established that treatment with Herceptin leads to selective overexpression and activation of epidermal growth factor receptor (EGFR) and Src which further contributes to oncogenesis in Herceptin resistant and triple negative breast cancer (TNBC) patients. Here, we show a co-regulated upregulation in the expression of Annexin A2 (AnxA2), a known substrate of Src and one of the regulators of EGFR receptor endocytosis, in Herceptin resistant and Her-2 negative breast cancer. Immunohistochemical expression analysis revealed a reciprocal regulation between Her-2 and AnxA2 in breast cancer clinical samples as well as in cell lines as confirmed by protein and RNA analysis. The siRNA and Herceptin mediated downregulation/inhibition of Her-2 in Her-2 amplified cells induced AnxA2 expression and membrane translocation. In this study we report a possible involvement of AnxA2 in maintaining constitutively activated EGFR downstream signaling intermediates and hence in cell proliferation, migration and viability. This effect was consistent in Herceptin resistant JIMT-1 cells as well as in Her-2 negative breast cancer. The siRNA mediated AnxA2 downregulation leads to increased apoptosis, decreased cell viability and migration. Our studies further indicate the role of AnxA2 in EGFR-Src membrane bound signaling complex and ligand induced activation of downstream signaling pathways. Targeting this AnxA2 dependent positive regulation of EGFR signaling cascade may be of therapeutic value in Her-2 negative breast cancer. ItemFactors Associated with Attention Deficit/Hyperactivity Disorder Among US Children: Results from a National Survey(BioMedCentral, 2012-05-14) Lingineni, R. K.; Biswas, Swati; Ahmad, N.; Jackson, B. E.; Bae, S.; Singh, K. P.; 0000 0001 2704 188X (Biswas, S)Background: The purpose of this study was to investigate the association between Attention Deficit/Hyperactivity Disorder (ADHD) and various factors using a representative sample of US children in a comprehensive manner. This includes variables that have not been previously studied such as watching TV/playing video games, computer usage, family member's smoking, and participation in sports. Methods: This was a cross-sectional study of 68, 634 children, 5-17 years old, from the National Survey of Children's Health (NSCH, 2007-2008). We performed bivariate and multivariate logistic regression analyses with ADHD classification as the response variable and the following explanatory variables: sex, race, depression, anxiety, body mass index, healthcare coverage, family structure, socio-economic status, family members' smoking status, education, computer usage, watching television (TV)/playing video games, participation in sports, and participation in clubs/organizations. Results: Approximately 10% of the sample was classified as having ADHD. We found depression, anxiety, healthcare coverage, and male sex of child to have increased odds of being diagnosed with ADHD. One of the salient features of this study was observing a significant association between ADHD and variables such as TV usage, participation in sports, two-parent family structure, and family members' smoking status. Obesity was not found to be significantly associated with ADHD, contrary to some previous studies. Conclusions: The current study uncovered several factors associated with ADHD at the national level, including some that have not been studied earlier in such a setting. However, we caution that due to the cross-sectional and observational nature of the data, a cause and effect relationship between ADHD and the associated factors can not be deduced from this study. Future research on ADHD should take into consideration these factors, preferably through a longitudinal study design. © 2012 Lingineni et al.; licensee BioMed Central Ltd.