Digital Commons Network^™

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Duration Of Symptoms Resulting From Lumbar Disc Herniation: Effect On Treatment Outcomes: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Alan Hilibrand, Kristen Radcliff, Mark Kurd, Jon Lurie, Emily Blood, Todd J Albert, James N Weinstein

Rothman Institute Papers

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up …

Duration Of Symptoms Resulting From Lumbar Disc Herniation: Effect On Treatment Outcomes: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Alan S Hilibrand, Kristen Radcliff, Mark Kurd, Jon Lurie, Emily Blood, Todd J Albert, James N Weinstein

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up …

Pre- And Post-Bronchodilator Lung Function As Predictors Of Mortality In The Lung Health Study, David M. Mannino, Enrique Diaz-Guzman, Sonia Buist

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is supposed to be classified on the basis of post-bronchodilator lung function. Most longitudinal studies of COPD, though, do not have post-bronchodilator lung function available. We used pre-and post bronchodilator lung function data from the Lung Health Study to determine whether these measures differ in their ability to predict mortality.

METHODS: We limited our analysis to subjects who were of black or white race, on whom we had complete data, and who participated at either the 1 year or the 5 year follow-up visit. We classified subjects based on their baseline lung function, according …

Microarray-Based Cancer Prediction Using Single Genes., Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Although numerous methods of using microarray data analysis for cancer classification have been proposed, most utilize many genes to achieve accurate classification. This can hamper interpretability of the models and ease of translation to other assay platforms. We explored the use of single genes to construct classification models. We first identified the genes with the most powerful univariate class discrimination ability and then constructed simple classification rules for class prediction using the single genes.

RESULTS: We applied our model development algorithm to eleven cancer gene expression datasets and compared classification accuracy to that for standard methods including Diagonal Linear …

Regional Gray Matter Correlates Of Perceived Emotional Intelligence, Nancy S. Koven, Robert M. Roth, Matthew A. Garlinghouse, Laura A. Flashman, Andrew J. Saykin

Dartmouth Scholarship

Coping with stressful life events requires a degree of skill in the ability to attend to, comprehend, label, communicate and regulate emotions. Individuals vary in the extent to which these skills are developed, with the term ‘alexithymia’ often applied in the clinical and personality literature to those individuals most compromised in these skills. Although a frontal lobe model of alexithymia is emerging, it is unclear whether such a model satisfactorily reflects brain-related patterns associated with perceived emotional intelligence at the facet level. To determine whether these trait meta-mood facets (ability to attend to, have clarity of and repair emotions) have …

Ethics And The 'Seasons Of My Life' As A Dental Educator, David A. Nash

Oral Health Science Faculty Publications

Perhaps the first comprehensive ethics program in American dental schools was created in 1990 at the University of Kentucky by then dean David Nash. Nash recounts the emergence of his personal and professional interest in ethics using the structure of Daniel Levinson's book The Seasons of a Man's Life. Each season brings tasks of evolving and deepening ethical engagement. Being ethical is important; helping others to be so is special. Nash still teaches the course.

Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina

Kimmel Cancer Center Faculty Papers

BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to …

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

Supplier-Induced Demand For Psychiatric Admissions In Northern New England, Bradley V. Watts, Brian Shiner, Gunnar Klauss, William B. Weeks

Dartmouth Scholarship

The development of hospital service areas (HSAs) using small area analysis has been useful in examining variation in medical and surgical care; however, the techniques of small area analysis are underdeveloped in understanding psychiatric admission rates. We sought to develop these techniques in order to understand the relationship between psychiatric bed supply and admission rates in Northern New England. Our primary hypotheses were that there would be substantial variation in psychiatric admission across geographic settings and that bed availability would be positively correlated with admission rates, reflecting a supplier-induced demand phenomenon. Our secondary hypothesis was that the construction of psychiatric …

The Meaning Of Breast Cancer Risk For African American Women., Janice Phillips, Marlene Z. Cohen

Journal Articles: College of Nursing

PURPOSE: To describe African American women's experience of being at high risk for breast cancer.

DESIGN: A hermeneutic phenomenological approach was used to guide in-depth interviews and analysis. Methods to ensure trustworthiness and rigor were included.

METHODS: Open interviews were conducted with 20 African American women who were at high risk for breast cancer (family history, personal history, genetic mutation). They were recruited from a cancer risk clinic and community-based settings. Data were transcribed verbatim, and themes were labeled among and between all interviews.

FINDINGS: Five themes were identified: (a) life-changing experience; (b) relationships: fears, support, and concerns; (c) the …

Effect Of Variable Transmission Rate On The Dynamics Of Hiv In Sub-Saharan Africa, Diego F. Cuadros, Phillip H. Crowley, Ben Augustine, Sarah L. Stewart, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: The cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has been estimated to have a very low probability; but effects of cofactors that vary in space and time may substantially alter this pattern.

METHODS: To test the effect of individual variation in the HIV infectiousness generated by co-infection, we developed and analyzed a mathematical sexual network model that simulates the behavioral components of a population from Malawi, as well as the dynamics of HIV and the co-infection effect caused by other infectious diseases, …

Tlr4 Mutation Reduces Microglial Activation, Increases Aβ Deposits And Exacerbates Cognitive Deficits In A Mouse Model Of Alzheimer's Disease, Min Song, Jingji Jin, Jinghong Kou, Abhinandan Pattanayak, Jamaal Rehman, Hong-Duck Kim, Ken-Ichiro Fukuchi

NYMC Faculty Publications

BACKGROUND: Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD), are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs), a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it …

The Incidence Of Deep Vein Thrombosis Detected By Routine Surveillance Ultrasound In Neurosurgery Patients Receiving Dual Modality Prophylaxis., Patricia C Henwood, Thomas M Kennedy, Lynda Thomson, Taki Galanis, George L Tzanis, Geno J Merli, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The optimal method of thromboprophylaxis and the value of screening ultrasonography for detection of deep venous thrombosis (DVT) in neurosurgery patients remains unclear. The goal of this study was to determine the incidence of DVT in neurosurgical patients who, by hospital protocol, receive surveillance ultrasonography of the lower extremities twice weekly, in addition to prophylaxis with unfractionated heparin and external pneumatic compression sleeves. A retrospective review of 7,298 ultrasound studies carried out on 2,593 patients over 4 years at a university neurosurgical hospital was conducted. There was a 7.4% incidence of proximal lower extremity DVT and a 9.7% total incidence …

Classification And Treatment Of Proximal Humerus Fractures: Inter-Observer Reliability And Agreement Across Imaging Modalities And Experience., Abtin Foroohar, Rick Tosti, John M Richmond, John P Gaughan, Asif M Ilyas

Rothman Institute Papers

SUMMARY: Proximal humerus fractures (PHF) are common injuries, but previous studies have documented poor inter-observer reliability in fracture classification. This disparity has been attributed to multiple variables including poor imaging studies and inadequate surgeon experience. The purpose of this study is to evaluate whether inter-observer agreement can be improved with the application of multiple imaging modalities including X-ray, CT, and 3D CT reconstructions, stratified by physician experience, for both classification and treatment of PHFs.

METHODS: Inter-observer agreement was measured for classification and treatment of PHFs. A total of sixteen fractures were imaged by plain X-ray (scapular AP and lateral), CT …

Lafora Disease E3-Ubiquitin Ligase Malin Is Related To Trim32 At Both The Phylogenetic And Functional Level, Carlos Romá-Mateo, Daniel Moreno, Santiago Vernia, Teresa Rubio, Travis M. Bridges, Matthew S. Gentry, Pascual Sanz

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin.

RESULTS: After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming …

Genetic Determinants Of Uv-Susceptibility In Non-Melanoma Skin Cancer, Marleen M. Welsh, Margaret R. Karagas, Jacquelyn K. Kuriger, Andres Houseman, Steven K. Spencer, Ann E. Perry, Heather H. Nelson

Dartmouth Scholarship

A milieu of cytokines and signaling molecules are involved in the induction of UV-induced immune suppression and thus the etiology of non-melanoma skin cancer (NMSC). Targeting the UV-induced immunosuppression pathway, and using a large population based study of NMSC, we have investigated the risk associated with functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, and HAL). The most prominent single genetic effect was observed for IL10. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with …

Decision Quality Instrument For Treatment Of Hip And Knee Osteoarthritis: A Psychometric Evaluation, Karen R. Sepucha, Dawn Stacey, Catharine F. Clay, Yuchiao Chang

Dartmouth Scholarship

A high quality decision requires that patients who meet clinical criteria for surgery are informed about the options (including non-surgical alternatives) and receive treatments that match their goals. The aim of this study was to evaluate the psychometric properties and clinical sensibility of a patient self report instrument, to measure the quality of decisions about total joint replacement for knee or hip osteoarthritis.

Uncover Disease Genes By Maximizing Information Flow In The Phenome-Interactome Network., Yong Chen, Tao Jiang, Rui Jiang

College of Science & Mathematics Departmental Research

MOTIVATION: Pinpointing genes that underlie human inherited diseases among candidate genes in susceptibility genetic regions is the primary step towards the understanding of pathogenesis of diseases. Although several probabilistic models have been proposed to prioritize candidate genes using phenotype similarities and protein-protein interactions, no combinatorial approaches have been proposed in the literature.

RESULTS: We propose the first combinatorial approach for prioritizing candidate genes. We first construct a phenome-interactome network by integrating the given phenotype similarity profile, protein-protein interaction network and associations between diseases and genes. Then, we introduce a computational method called MAXIF to maximize the information flow in this …

Societal Expectations And The Profession's Responsibility To Reform The Dental Workforce To Ensure Access To Care For Children, David A. Nash

Oral Health Science Faculty Publications

Societal expectations raise the issue of the nature of a profession and a profession's relationship with society. Influential policy leaders want reform of the oral health workforce and delivery system in such a manner as to ensure that improvements are made for accessing care, particularly for vulnerable and disadvantaged populations, especially children. This essay is based on a presentation to the House of Delegates of the California Dental Association on Nov.13, 2009.

Marital Status And Survival In Pancreatic Cancer Patients: A Seer Based Analysis., Michael J. Baine, Freshta Sahak, Chi Lin, Subhankar Chakraborty, Surinder K. Batra, Elizabeth R. Lyden

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Recent findings suggest that marital status affects survival in patients with different types of cancer. However, its role in the survival of patients with pancreatic ductal adenocarcinoma is unknown. In this study, we investigated whether there was an association between marital status and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: Adult patients diagnosed with PDAC between 1998 and 2003 with known marital statuses were identified from the Surveillance, Epidemiology, and End Results registry of the National Cancer Institute. OS for these patients was plotted using the Kaplan-Meier method. Comparative risks of mortality were evaluated by …

Tnfα Enhances The Motility And Invasiveness Of Prostatic Cancer Cells By Stimulating The Expression Of Selective Glycosyl- And Sulfotransferase Genes Involved In The Synthesis Of Selectin Ligands., Prakash Radhakrishnan, Vishwanath Chachadi, Ming-Fong Lin, Rakesh Singh, Reiji Kannagi, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Sialyl Lewis x (sLe(x)) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLe(x) antibody, and anti-6-sulfo-sialyl Lewis x …

Outcomes Of Treatment For Hepatitis C Virus Infection By Primary Care Providers, Sanjeev Arora, Karla Thornton, Glen Murata, Paulina Deming, Summers Kalishman, Denise Dion, Brooke Parish, Thomas Burke, Wesley Pak, Jeffrey Dunkelberg, Martin Kistin, John Brown, Steven Jenkusky, Miriam Komaromy, Clifford Qualls

Project ECHO Bibliography

BACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was developed to improve access to care for underserved populations with complex health problems such as hepatitis C virus (HCV) infection. With the use of video-conferencing technology, the ECHO program trains primary care providers to treat complex diseases.

METHODS: We conducted a prospective cohort study comparing treatment for HCV infection at the University of New Mexico (UNM) HCV clinic with treatment by primary care clinicians at 21 ECHO sites in rural areas and prisons in New Mexico. A total of 407 patients with chronic HCV infection who had received no previous …

Remote Positioning Optical Breast Magnetic Resonance Coil For Slice-Selection During Image-Guided Near-Infrared Spectroscopy Of Breast Cancer, Michael A. Mastanduno, Shudong Jiang, Brian W. Pogue, Keith D. Paulsen, Roberta Diflorio-Alexander

Dartmouth Scholarship

The design and testing of a pneumatic optical positioning interface produced with the goal of improving fiber positioning in magnetic resonance (MR)-guided diffuse spectral imaging of breast cancer is presented. The system was created for vertical positioning of optical fibers inside the MR bore during a patient exam to target suspicious lesions with MR scans for reference and collect multiple planes of optical data. The interface includes new fiber plates for mechanical and optical coupling to the breast, and was tested in phantoms and human imaging. Reconstructions with data taken in the new interface show acceptable linearity over different absorber …

Endothelial Differentiation Of Adipose-Derived Stem Cells From Elderly Patients With Cardiovascular Disease., Ping Zhang, Neil Moudgill, Eric Hager, Nicolas Tarola, Christopher Dimatteo, Stephen Mcilhenny, Thomas Tulenko, Paul J Dimuzio

Department of Surgery Faculty Papers

Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, …

Recombination Phenotypes Of The Nci-60 Collection Of Human Cancer Cells, Dawn M. Stults, Michael W. Killen, Brent J. Shelton, Andrew J. Pierce

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60.

RESULTS: We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of …

Nfatc1 Regulation Of Trail Expression In Human Intestinal Cells, Qingding Wang, Yuning Zhou, Heidi L. Weiss, Chi-Wing Chow, B. Mark Evers

Surgery Faculty Publications

TNF-related apoptosis-inducing ligand (TRAIL; Apo2) has been shown to promote intestinal cell differentiation. Nuclear factor of activated T cells (NFAT) participates in the regulation of a variety of cellular processes, including differentiation. Here, we examined the role of NFAT in the regulation of TRAIL in human intestinal cells. Treatment with a combination of phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187 (Io) increased NFAT activation and TRAIL expression; pretreatment with the calcineurin inhibitor cyclosporine A (CsA), an antagonist of NFAT signaling, diminished NFAT activation and TRAIL induction. In addition, knockdown of NFATc1, NFATc2, NFATc3, and NFATc4 blocked PMA/Io increased …

Septin Filaments Exhibit A Dynamic, Paired Organization That Is Conserved From Yeast To Mammals, Bradley S. Demay, Xiaobo Bai, Louisa Howard, Patricia Occhipinti, Rebecca A. Meseroll, Elias T. Spiliotis, Rudolf Oldenbourg, Amy S. Gladfelter

Dartmouth Scholarship

The septins are conserved, GTP-binding proteins important for cytokinesis, membrane compartmentalization, and exocytosis. However, it is unknown how septins are arranged within higher-order structures in cells. To determine the organization of septins in live cells, we developed a polarized fluorescence microscopy system to monitor the orientation of GFP dipole moments with high spatial and temporal resolution. When GFP was fused to septins, the arrangement of GFP dipoles reflected the underlying septin organization. We demonstrated in a filamentous fungus, a budding yeast, and a mammalian epithelial cell line that septin proteins were organized in an identical highly ordered fashion. Fluorescence anisotropy …

Mitostatin Is Down-Regulated In Human Prostate Cancer And Suppresses The Invasive Phenotype Of Prostate Cancer Cells., Matteo Fassan, Domenico D'Arca, Juraj Letko, Andrea Vecchione, Marina P Gardiman, Peter Mccue, Bernadette Wildemore, Massimo Rugge, Dolores Shupp-Byrne, Leonard G Gomella, Andrea Morrione, Renato V Iozzo, Raffaele Baffa

Kimmel Cancer Center Faculty Papers

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in …

Domainrbf: A Bayesian Regression Approach To The Prioritization Of Candidate Domains For Complex Diseases., Wangshu Zhang, Yong Chen, Fengzhu Sun, Rui Jiang

College of Science & Mathematics Departmental Research

BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named "domainRBF" (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases.

RESULTS: Using a compiled dataset containing 1,614 …