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1.  Genomic Promoter Analysis Predicts Functional Transcription Factor Binding 
Advances in bioinformatics  2008;2008:3698301-3698309.
The computational identification of functional transcription factor binding sites (TFBSs) remains a major challenge of computational biology.
We have analyzed the conserved promoter sequences for the complete set of human RefSeq genes using our conserved transcription factor binding site (CONFAC) software. CONFAC identified 16296 human-mouse ortholog gene pairs, and of those pairs, 9107 genes contained conserved TFBS in the 3 kb proximal promoter and first intron. To attempt to predict in vivo occupancy of transcription factor binding sites, we developed a novel marginal effect isolator algorithm that builds upon Bayesian methods for multigroup TFBS filtering and predicted the in vivo occupancy of two transcription factors with an overall accuracy of 84%.
Our analyses show that integration of chromatin immunoprecipitation data with conserved TFBS analysis can be used to generate accurate predictions of functional TFBS. They also show that TFBS cooccurrence can be used to predict transcription factor binding to promoters in vivo.
PMCID: PMC2768302  PMID: 19865592
2.  Genomic Promoter Analysis Predicts Functional Transcription Factor Binding 
Advances in Bioinformatics  2008;2008:369830.
Background. The computational identification of functional transcription factor binding sites (TFBSs) remains a major challenge of computational biology. Results. We have analyzed the conserved promoter sequences for the complete set of human RefSeq genes using our conserved transcription factor binding site (CONFAC) software. CONFAC identified 16296 human-mouse ortholog gene pairs, and of those pairs, 9107 genes contained conserved TFBS in the 3 kb proximal promoter and first intron. To attempt to predict in vivo occupancy of transcription factor binding sites, we developed a novel marginal effect isolator algorithm that builds upon Bayesian methods for multigroup TFBS filtering and predicted the in vivo occupancy of two transcription factors with an overall accuracy of 84%. Conclusion. Our analyses show that integration of chromatin immunoprecipitation data with conserved TFBS analysis can be used to generate accurate predictions of functional TFBS. They also show that TFBS cooccurrence can be used to predict transcription factor binding to promoters in vivo.
PMCID: PMC2768302  PMID: 19865592
3.  Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms 
Nature Communications  2016;7:11220.
Many bacteria produce extracellular and surface-associated components such as membrane vesicles (MVs), extracellular DNA and moonlighting cytosolic proteins for which the biogenesis and export pathways are not fully understood. Here we show that the explosive cell lysis of a sub-population of cells accounts for the liberation of cytosolic content in Pseudomonas aeruginosa biofilms. Super-resolution microscopy reveals that explosive cell lysis also produces shattered membrane fragments that rapidly form MVs. A prophage endolysin encoded within the R- and F-pyocin gene cluster is essential for explosive cell lysis. Endolysin-deficient mutants are defective in MV production and biofilm development, consistent with a crucial role in the biogenesis of MVs and liberation of extracellular DNA and other biofilm matrix components. Our findings reveal that explosive cell lysis, mediated through the activity of a cryptic prophage endolysin, acts as a mechanism for the production of bacterial MVs.
Many bacteria release DNA and membrane vesicles through unclear mechanisms. Here, the authors show that a prophage endolysin is involved in the explosive lysis of a sub-population of cells in Pseudomonas aeruginosa, releasing cytoplasmic content and membrane fragments that rapidly form membrane vesicles.
PMCID: PMC4834629  PMID: 27075392
4.  Mental Health Smartphone Apps: Review and Evidence-Based Recommendations for Future Developments 
JMIR Mental Health  2016;3(1):e7.
The number of mental health apps (MHapps) developed and now available to smartphone users has increased in recent years. MHapps and other technology-based solutions have the potential to play an important part in the future of mental health care; however, there is no single guide for the development of evidence-based MHapps. Many currently available MHapps lack features that would greatly improve their functionality, or include features that are not optimized. Furthermore, MHapp developers rarely conduct or publish trial-based experimental validation of their apps. Indeed, a previous systematic review revealed a complete lack of trial-based evidence for many of the hundreds of MHapps available.
To guide future MHapp development, a set of clear, practical, evidence-based recommendations is presented for MHapp developers to create better, more rigorous apps.
A literature review was conducted, scrutinizing research across diverse fields, including mental health interventions, preventative health, mobile health, and mobile app design.
Sixteen recommendations were formulated. Evidence for each recommendation is discussed, and guidance on how these recommendations might be integrated into the overall design of an MHapp is offered. Each recommendation is rated on the basis of the strength of associated evidence. It is important to design an MHapp using a behavioral plan and interactive framework that encourages the user to engage with the app; thus, it may not be possible to incorporate all 16 recommendations into a single MHapp.
Randomized controlled trials are required to validate future MHapps and the principles upon which they are designed, and to further investigate the recommendations presented in this review. Effective MHapps are required to help prevent mental health problems and to ease the burden on health systems.
PMCID: PMC4795320  PMID: 26932350
mobile phones; mental health; smartphones; apps; mobile apps; depression; anxiety; cognitive behavior therapy; cognitive behavioral therapy; clinical psychology
5.  Comparison of EBT and EBT3 RadioChromic Film Usage in Parotid Cancer Radiotherapy 
EBT and EBT3 radioChromic films have been used in radiotherapy dosimetry for years.
The aim of the current study is to compare EBT and EBT3 radioChromic films in dosimetry of radiotherapy fields for treatment of parotid cancer.
Calibrations of EBT and EBT3 films were performed with identical setups using a 6 MV photon beam of a Siemens Primus linac. Skin dose was measured at different points in the right anterior oblique (RAO) and right posterior oblique (RPO) fields by EBT and EBT3 films on a RANDO phantom.
While dosimetry was performed with the same conditions for the two film types for calibration and in phantom in parotid cancer radiotherapy, the measured net optical density (NOD) in EBT film was found to be higher than that from EBT3 film. The minimum difference between these two films under calibration conditions was about 2.9% (for 0.2 Gy) with a maximum difference of 35.5% (for 0.5 Gy). In the therapeutic fields of parotid cancer radiotherapy at different points, the measured dose from EBT film was higher than the EBT3 film. In these fields the minimum and maximum measured dose differences were 16.0% and 25.5%, respectively.
EBT film demonstrates higher NOD than EBT3 film. This effect may be related to the higher sensitivity of EBT film over EBT3 film. However, the obtained dose differences between these two films in low dose range can be due to the differences in fitting functions applied following the calibration process.
PMCID: PMC4795323  PMID: 27026949
RadioChromic film; EBT; EBT3; Radiotherapy; Parotid cancer
6.  Designing mucoadhesive discs containing stem bark extract of Ziziphus jujuba based on Iranian traditional documents 
Objective (s):
Mucoadhesive disc is one of the various routes of drug delivery for curing buccal disease
Materials and Methods:
Every discs containing 70 mg stem bark extract of Ziziphus jujuba were formulated by using Carbopol 934, PVP k30 and gelatin as polymers. Discs were made by granulation and direct compression. Discs were standardized based on the total phenol. Properties such as in vitro and in vivo mucoadhesion, drug release, water uptake, and disintegration were carried out.
Discs showed excellent mucoadhesion and released high amount of the active ingredients (47%) immediately and completed after approximately the first hour. They had a good adhesion in buccal cavity.
This study showed that the kinetics of release of the active substance from the mucoadhesive disc obeyed the zero order kinetic and didn’t follow the fick's law. The water uptake and dissolution (DS), increased with the passing of time.
PMCID: PMC4834124  PMID: 27114804
Carbopol 934; Mucoadhesive discs; Pharmaceutical tests; PVP(Polyvinylpyrrolidone); Ziziphus jujuba stem bark
7.  Effects of combined β-hydroxy-β-methylbutyrate (HMB) and whey protein ingestion on symptoms of eccentric exercise-induced muscle damage 
The purpose of this study was to examine the effects of combined β-hydroxy-β-methylbutyrate (HMB) and whey protein ingestion on muscle strength and damage following a single bout of eccentric exercise.
Eighteen untrained male subjects were assigned to HMB and Whey protein (HMB + Whey; 3 g/day HMB and 36.6 g/day whey protein, n = 6), HMB (3 g/day, n = 6), or whey protein (36.6 g/day, n = 6) groups. Ingestion commenced 7 days before non-dominant elbow flexor eccentric exercise (30 deg/sec, 6 reps × 7 sets) and continued until 4 days post-exercise. The maximal isometric strength, muscle soreness, plasma creatine kinase (CK), lactate dehydrogenase (LDH) were assessed pre-exercise, and at 1, 2, 3, and 5 days after exercise.
The change scores of maximal isometric strength significantly decreased at day 1, 2, and 5 in the whey protein group compared to pre value and that in HMB + Whey protein and HMB groups decreased at day 1 and 5. The muscle soreness significantly increased in the whey and HMB + Whey protein groups at day 3 compared to pre value (p < 0.05). CK and LDH significantly increased (time effect: p < 0.05) after exercise. However, all data were not significant difference among the groups.
These results suggest that ingestion of combined HMB and whey protein does not have a role to inhibit muscle strength loss and soreness, and decrease in muscle damage markers after eccentric exercise in comparison with HMB and whey protein alone.
PMCID: PMC4772288  PMID: 26933398
Amino acids; Muscle strength; Lengthening; Muscle soreness
8.  Tactile Gap Detection Deteriorates during Bimanual Symmetrical Movements under Mirror Visual Feedback 
PLoS ONE  2016;11(1):e0146077.
It has been suggested that incongruence between signals for motor intention and sensory input can cause pain and other sensory abnormalities. This claim is supported by reports that moving in an environment of induced sensorimotor conflict leads to elevated pain and sensory symptoms in those with certain painful conditions. Similar procedures can lead to reports of anomalous sensations in healthy volunteers too. In the present study, we used mirror visual feedback to investigate the effects of sensorimotor incongruence on responses to stimuli that arise from sources external to the body, in particular, touch. Incongruence between the sensory and motor signals for the right arm was manipulated by having the participants make symmetrical or asymmetrical movements while watching a reflection of their left arm in a parasagittal mirror, or the left hand surface of a similarly positioned opaque board. In contrast to our prediction, sensitivity to the presence of gaps in tactile stimulation of the right forearm was not reduced when participants made asymmetrical movements during mirror visual feedback, as compared to when they made symmetrical or asymmetrical movements with no visual feedback. Instead, sensitivity was reduced when participants made symmetrical movements during mirror visual feedback relative to the other three conditions. We suggest that small discrepancies between sensory and motor information, as they occur during mirror visual feedback with symmetrical movements, can impair tactile processing. In contrast, asymmetrical movements with mirror visual feedback may not impact tactile processing because the larger discrepancies between sensory and motor information may prevent the integration of these sources of information. These results contrast with previous reports of anomalous sensations during exposure to both low and high sensorimotor conflict, but are nevertheless in agreement with a forward model interpretation of perceptual modulations during goal directed movement.
PMCID: PMC4701376  PMID: 26731117
9.  Biologic subtype is a more important prognostic factor than nodal involvement in patients with stages I and II breast carcinoma 
Nodal infiltration has been one of the most important prognostic factors in breast cancer. In recent decades, risk stratification has greatly changed, and is applied in accordance with hormone receptor and human epidermal growth factor receptor 2 (HER2) status. We compared the prognostic power of tumor subtype to nodal involvement in early breast cancer.
We reviewed the medical records of 505 patients who had curative surgery for stage I or II breast cancer. We analyzed clinicopathologic factors according to tumor subtype and nodal involvement. Tumors were classified into 4 subtypes according to immunohistochemical status of estrogen receptor, progesterone receptor, HER2, and Ki67 labeling index. Disease-free survival (DFS) and overall survival were analyzed.
There were 363 node-negative patients (71.9%) and 142 node-positive patients (28.1%). Luminal A, Luminal B, HER2, and triple-negative breast cancer subtypes were composed of 207 (41.0%), 147 (29.1%), 42 (8.3%), and 109 patients (21.6%), respectively. The median follow-up period was 89.5 months. Node negative-luminal A subtype showed the best prognosis with regard to 5-year DFS, and the pN1-triple negative subtype was associated with the shortest DFS (95.1% vs. 67.8%; hazard ratio, 9.554; P < 0.001). However, the node negative-triple negative subtype was associated with a worse 5-year DFS than the pN1-luminal A subtype ([86.4%; hazard ratio, 2.647; P = 0.048] vs. [93.2%; hazard ratio, 2.061; P = 0.194]).
Node negative-triple negative breast cancer was associated with a poorer prognosis than pN1-luminal A subtype. Tumor subtype has greater prognostic power compared to nodal status in early breast cancer.
PMCID: PMC4717602  PMID: 26793686
Breast neoplasms; Lymphatic metastasis; Prognosis; Triple negative breast neoplasms
10.  Does this baby have a tail?: a case of congenital isolated perineal lipoma presenting as human pseudo-tail 
A pseudo-tail is defined as a tail-like lesion in the lumbosacrococcygeal region that is not a true tail but one caused by disease. Perineal lipoma is one of the conditions that may present as a pseudo-tail. Congenital perineal lipoma is a rare disease and in particular, isolated congenital perineal lipoma without other anomalies is extremely rare. Here we report a case of congenital isolated perineal lipoma presenting as a pseudo-tail and also include a literature review of the condition.
PMCID: PMC4717609  PMID: 26793694
Tail; Pseudo-tail; Perineal lipoma; Infant; Lipoma
11.  A Report of the Women's Health Congress Workshop on The Health of Women of Color: A Critical Intersection at the Corner of Sex/Gender and Race/Ethnicity 
Journal of Women's Health  2016;25(1):4-10.
Women of color face unique health challenges that differ significantly from those of other women and men of color. To bring these issues to light, the National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop at the 23rd Annual Women's Health Congress, which was held in Washington, DC, in April 2015. The workshop featured presentations by NIH intramural and extramural scientists who provided insight on the disparities of a wide range of conditions, including cancer, cardiovascular disease, the risk of HIV infection, and disability in an aging population. In this study, we highlight the major points of each presentation and the ensuing discussion.
PMCID: PMC4741201  PMID: 26771559
12.  Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healing-associated genes 
Neural Regeneration Research  2016;11(1):144-149.
Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion (DRG) sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.
PMCID: PMC4774208  PMID: 26981104
acetaminophen; analgesics; axon; buprenorphine; dorsal root ganglia; gene expression; peripheral nerve injuries; regeneration; sciatic nerve; wound healing
13.  Adverse psychosocial outcomes associated with drug use among US high school seniors: a comparison of alcohol and marijuana 
There is debate about whether marijuana (cannabis) use is more dangerous than alcohol use. Although difficult to make objective comparisons, research is needed to compare relative dangers in order to help inform preventive efforts and policy.
Data were analyzed from a nationally representative sample of high school seniors in the Monitoring the Future study (2007–2011; Weighted n = 7437; modal age: 18) who reported lifetime use of alcohol or marijuana. Students were asked to indicate whether they experienced various adverse psychosocial outcomes resulting from use of each substance. We examined which outcomes were more prevalent for each substance.
Compared to alcohol use, marijuana use was more commonly reported to compromise relationships with teachers or supervisors, result in less energy or interest, and result in lower school or job performance. Compared to marijuana use, alcohol was more commonly reported to compromise relationships with friends and significant others; it was also reported to lead to more regret (particularly among females), and driving unsafely. Marijuana users were more likely to report no adverse outcomes. Females and white students were more likely to report various adverse outcomes and higher frequency use of each substance also increased occurrences of reported adverse outcomes.
Marijuana and alcohol are associated with unique adverse psychosocial outcomes. Outcomes differ by sex and race/ethnicity, and perception or experience of outcomes may also be related to legal status and associated stigma. Public health interventions may be more effective by focusing on harm reduction strategies for these drug-specific outcomes.
PMCID: PMC4687013  PMID: 25169838
Adolescents; adverse outcomes; alcohol; cannabis; marijuana
14.  A Literature Review and Case Report of Metastatic Pure Choriocarcinoma 
In 2012, testicular cancer was estimated to account for 940 disability adjusted life years in Australia; of these, 450 were years lost due to premature death and 500 were years of healthy life lost due to disease, disability, or injury (Australian Institute of Health and Welfare and Australasian Association of Cancer Registries, 2012). Testicular choriocarcinoma is one of the rarest variants of testicular germ cell tumours, accounting for less than 1% of testicular germ cell tumours and only about 0.19% of all testicular tumours. Management involves radical orchidectomy and chemotherapy. Even then, prognosis is poor. This case report describes a 20-year-old male with pure testicular choriocarcinoma with pulmonary metastases which showed sustained and complete response to adjuvant chemotherapy consisting of bleomycin, etoposide, and cisplatin.
PMCID: PMC4663315  PMID: 26649213
15.  Recent Advances in Learning Theory 
PMCID: PMC4663317  PMID: 26649035
16.  The cervical cancer prevention programme in Costa Rica 
ecancermedicalscience  2015;9:578.
Cervical and uterine cancer continues to be an important issue for women around the world, although neoplasia has the greatest demonstrated potential for prevention.
Costa Rica has achieved important advances in the reduction of the incidence and mortality of these cancers since the last century. This is the result of a series of policies, programmes, and plans, not only at the level of the health care system, but also in other areas.
Increased access for women to care in health centres, fundamentally at the primary level, has been vital, as has ensuring the quality of cytology readings and access to diagnosis and treatment for precursor lesions for in situ and invasive cancers.
Despite all of these achievements, there are still challenges to be overcome, which are widespread in many countries in Latin America and the Caribbean.
It is important to learn from the experiences of other countries in order to improve women’s health not only as a health objective, but also as an ethical imperative to promote the exercise of women’s rights to life and health.
PMCID: PMC4631572  PMID: 26557876
cervical cancer; prevention programme; early detection in Costa Rica
17.  Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo 
It is believed that senescent cells contribute to the progression of primary and metastatic tumors, however, the exact mechanisms of this activity remain elusive. In this report we show that senescent human peritoneal mesothelial cells (HPMCs) alter the secretory profile of ovarian cancer cells (A2780, OVCAR-3, SKOV-3) by increasing the release of four angiogenic agents: CXCL1, CXCL8, HGF, and VEGF. Proliferation and migration of endothelial cells subjected to conditioned medium generated by: cancer cells modified by senescent HPMCs; cancer cells co-cultured with senescent HPMCs; and by early-passage HPMCs from aged donors, were markedly intensified. The same was the case for the vascularization, size and number of tumors that developed in the mouse peritoneum upon injection of ovarian cancer cells with senescent HPMCs. When the identified pro-angiogenic proteins were neutralized in conditioned medium from the cancer cells, both aspects of endothelial cell behavior intensified in vitro in response to senescent HPMCs were markedly reduced. The search for mediators of senescent HPMC activity using specific neutralizing antibodies and recombinant exogenous proteins showed that the intensified angiogenic potential of cancer cells was elicited by IL-6 and TGF-β1. At the transcriptional level, increased proliferation and migration of endothelial cells exposed to cancer cells modified by senescent HPMCs was regulated by HIF-1α, NF-κB/p50 and AP-1/c-Jun. Collectively, our findings indicate that senescent HPMCs may promote the progression of ovarian cancer cells by reprogramming their secretory phenotype towards increased production of pro-angiogenic agents and subsequent increase in the angiogenic capabilities of the vascular endothelium.
PMCID: PMC4740564  PMID: 26433963
Angiogenesis; Cellular senescence; Mesothelial cells; Ovarian cancer; Peritoneal cavity
18.  The Contribution of Missense Mutations in Core and Rim Residues of Protein–Protein Interfaces to Human Disease 
Journal of Molecular Biology  2015;427(17):2886-2898.
Missense mutations at protein–protein interaction sites, called interfaces, are important contributors to human disease. Interfaces are non-uniform surface areas characterized by two main regions, “core” and “rim”, which differ in terms of evolutionary conservation and physicochemical properties. Moreover, within interfaces, only a small subset of residues (“hot spots”) is crucial for the binding free energy of the protein–protein complex.
We performed a large-scale structural analysis of human single amino acid variations (SAVs) and demonstrated that disease-causing mutations are preferentially located within the interface core, as opposed to the rim (p < 0.01). In contrast, the interface rim is significantly enriched in polymorphisms, similar to the remaining non-interacting surface. Energetic hot spots tend to be enriched in disease-causing mutations compared to non-hot spots (p = 0.05), regardless of their occurrence in core or rim residues. For individual amino acids, the frequency of substitution into a polymorphism or disease-causing mutation differed to other amino acids and was related to its structural location, as was the type of physicochemical change introduced by the SAV.
In conclusion, this study demonstrated the different distribution and properties of disease-causing SAVs and polymorphisms within different structural regions and in relation to the energetic contribution of amino acid in protein–protein interfaces, thus highlighting the importance of a structural system biology approach for predicting the effect of SAVs.
Graphical abstract
•Protein–protein interactions are fundamental in all biological processes.•The distribution of deleterious and non-SAVs within protein interfaces is unknown.•The distribution of deleterious SAVs differs within different interface structural regions.•The distribution of SAVs differs in relation to interface residues energetic contribution.•Structural analysis of protein complexes enhances the understanding of deleterious SAVs.
PMCID: PMC4548493  PMID: 26173036
ASMT, acetyl serotonin O-methyltransferase; PDB, Protein Data Bank; SPT, serine pyruvate aminotransferase; PLCE1, 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1; PPI, protein–protein interaction; SAV, single amino acid variation; SSE, secondary structure elements; protein–protein interaction; core and rim interface; human disease; SAVs; nsSNPs
19.  The Combinational Polymorphisms of ORAI1 Gene Are Associated with Preventive Models of Breast Cancer in the Taiwanese 
BioMed Research International  2015;2015:281263.
The ORAI calcium release-activated calcium modulator 1 (ORAI1) has been proven to be an important gene for breast cancer progression and metastasis. However, the protective association model between the single nucleotide polymorphisms (SNPs) of ORAI1 gene was not investigated. Based on a published data set of 345 female breast cancer patients and 290 female controls, we used a particle swarm optimization (PSO) algorithm to identify the possible protective models of breast cancer association in terms of the SNPs of ORAI1 gene. Results showed that the PSO-generated models of 2-SNP (rs12320939-TT/rs12313273-CC), 3-SNP (rs12320939-TT/rs12313273-CC/rs712853-(TT/TC)), 4-SNP (rs12320939-TT/rs12313273-CC/rs7135617-(GG/GT)/rs712853-(TT/TC)), and 5-SNP (rs12320939-TT/rs12313273-CC/rs7135617-(GG/GT)/rs6486795-CC/rs712853-(TT/TC)) displayed low values of odds ratios (0.409–0.425) for breast cancer association. Taken together, these results suggested that our proposed PSO strategy is powerful to identify the combinational SNPs of rs12320939, rs12313273, rs7135617, rs6486795, and rs712853 of ORAI1 gene with a strongly protective association in breast cancer.
PMCID: PMC4561876  PMID: 26380267
20.  Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada 
Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of overdiagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40 year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55-69, to $588,300/LYG, for screening every two years from ages 40-74. The marginal benefits of increasing screening frequency to two years or starting screening at age 40 were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of QALYs; however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration.
PMCID: PMC4410808  PMID: 24443367
prostate cancer; PSA testing; screening; cost-effectiveness
21.  A Review of Feature Selection and Feature Extraction Methods Applied on Microarray Data 
Advances in Bioinformatics  2015;2015:198363.
We summarise various ways of performing dimensionality reduction on high-dimensional microarray data. Many different feature selection and feature extraction methods exist and they are being widely used. All these methods aim to remove redundant and irrelevant features so that classification of new instances will be more accurate. A popular source of data is microarrays, a biological platform for gathering gene expressions. Analysing microarrays can be difficult due to the size of the data they provide. In addition the complicated relations among the different genes make analysis more difficult and removing excess features can improve the quality of the results. We present some of the most popular methods for selecting significant features and provide a comparison between them. Their advantages and disadvantages are outlined in order to provide a clearer idea of when to use each one of them for saving computational time and resources.
PMCID: PMC4480804  PMID: 26170834
22.  Semantic Annotation for Biological Information Retrieval System 
Advances in Bioinformatics  2015;2015:597170.
Online literatures are increasing in a tremendous rate. Biological domain is one of the fast growing domains. Biological researchers face a problem finding what they are searching for effectively and efficiently. The aim of this research is to find documents that contain any combination of biological process and/or molecular function and/or cellular component. This research proposes a framework that helps researchers to retrieve meaningful documents related to their asserted terms based on gene ontology (GO). The system utilizes GO by semantically decomposing it into three subontologies (cellular component, biological process, and molecular function). Researcher has the flexibility to choose searching terms from any combination of the three subontologies. Document annotation is taking a place in this research to create an index of biological terms in documents to speed the searching process. Query expansion is used to infer semantically related terms to asserted terms. It increases the search meaningful results using the term synonyms and term relationships. The system uses a ranking method to order the retrieved documents based on the ranking weights. The proposed system achieves researchers' needs to find documents that fit the asserted terms semantically.
PMCID: PMC4337267  PMID: 25737720
23.  A Highly Conserved GEQYQQLR Epitope Has Been Identified in the Nucleoprotein of Ebola Virus by Using an In Silico Approach 
Advances in Bioinformatics  2015;2015:278197.
Ebola virus (EBOV) is a deadly virus that has caused several fatal outbreaks. Recently it caused another outbreak and resulted in thousands afflicted cases. Effective and approved vaccine or therapeutic treatment against this virus is still absent. In this study, we aimed to predict B-cell epitopes from several EBOV encoded proteins which may aid in developing new antibody-based therapeutics or viral antigen detection method against this virus. Multiple sequence alignment (MSA) was performed for the identification of conserved region among glycoprotein (GP), nucleoprotein (NP), and viral structural proteins (VP40, VP35, and VP24) of EBOV. Next, different consensus immunogenic and conserved sites were predicted from the conserved region(s) using various computational tools which are available in Immune Epitope Database (IEDB). Among GP, NP, VP40, VP35, and VP30 protein, only NP gave a 100% conserved GEQYQQLR B-cell epitope that fulfills the ideal features of an effective B-cell epitope and could lead a way in the milieu of Ebola treatment. However, successful in vivo and in vitro studies are prerequisite to determine the actual potency of our predicted epitope and establishing it as a preventing medication against all the fatal strains of EBOV.
PMCID: PMC4331325  PMID: 25709646
24.  Development of a Machine Learning Method to Predict Membrane Protein-Ligand Binding Residues Using Basic Sequence Information 
Advances in Bioinformatics  2015;2015:843030.
Locating ligand binding sites and finding the functionally important residues from protein sequences as well as structures became one of the challenges in understanding their function. Hence a Naïve Bayes classifier has been trained to predict whether a given amino acid residue in membrane protein sequence is a ligand binding residue or not using only sequence based information. The input to the classifier consists of the features of the target residue and two sequence neighbors on each side of the target residue. The classifier is trained and evaluated on a nonredundant set of 42 sequences (chains with at least one transmembrane domain) from 31 alpha-helical membrane proteins. The classifier achieves an overall accuracy of 70.7% with 72.5% specificity and 61.1% sensitivity in identifying ligand binding residues from sequence. The classifier performs better when the sequence is encoded by psi-blast generated PSSM profiles. Assessment of the predictions in the context of three-dimensional structures of proteins reveals the effectiveness of this method in identifying ligand binding sites from sequence information. In 83.3% (35 out of 42) of the proteins, the classifier identifies the ligand binding sites by correctly recognizing more than half of the binding residues. This will be useful to protein engineers in exploiting potential residues for functional assessment.
PMCID: PMC4329842  PMID: 25802517
25.  PhosphoHunter: An Efficient Software Tool for Phosphopeptide Identification 
Advances in Bioinformatics  2015;2015:382869.
Phosphorylation is a protein posttranslational modification. It is responsible of the activation/inactivation of disease-related pathways, thanks to its role of “molecular switch.” The study of phosphorylated proteins becomes a key point for the proteomic analyses focused on the identification of diagnostic/therapeutic targets. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the most widely used analytical approach. Although unmodified peptides are automatically identified by consolidated algorithms, phosphopeptides still require automated tools to avoid time-consuming manual interpretation. To improve phosphopeptide identification efficiency, a novel procedure was developed and implemented in a Perl/C tool called PhosphoHunter, here proposed and evaluated. It includes a preliminary heuristic step for filtering out the MS/MS spectra produced by nonphosphorylated peptides before sequence identification. A method to assess the statistical significance of identified phosphopeptides was also formulated. PhosphoHunter performance was tested on a dataset of 1500 MS/MS spectra and it was compared with two other tools: Mascot and Inspect. Comparisons demonstrated that a strong point of PhosphoHunter is sensitivity, suggesting that it is able to identify real phosphopeptides with superior performance. Performance indexes depend on a single parameter (intensity threshold) that users can tune according to the study aim. All the three tools localized >90% of phosphosites.
PMCID: PMC4309027  PMID: 25653679

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