Friday, January 23, 2015

Interview with Jie Zheng

This author interview is by Dr Jie Zheng, of Nanyang Technological University, Singapore. Dr Zheng's full paper, In Silico Prediction of Synthetic Lethality by Meta-Analysis of Genetic Interactions, Functions, and Pathways in Yeast and Human Cancer, is available for download in Cancer Informatics.


Please summarise for readers the content of your article.
A pair of genes is called synthetic lethality (SL) if mutations of both genes will kill a cell while mutation of either gene alone will not. Hence, a gene in SL interactions with a cancer-specific mutated gene will be a promising drug target with anti-cancer selectivity. As wet-lab screening approaches are still expensive, computational methods are important for large-scale discovery of SL interactions.

In this article, we proposed a computational approach named MetaSL for predicting yeast SL, which integrates 17 genomic and proteomic features and the outputs of 10 classification methods. We also conducted analysis for feature ranking output by MetaSL, which provided biological insights into the observed SL in yeast. Moreover, through orthologous mapping from yeast to human genes, we then predicted several lists of candidate SL pairs in human cancer.

How did you come to be involved in your area of study?
When I was a postdoc researcher at USA National Institutes of Health, I worked on recombination hotspots in human genomes. After moving to Singapore as a junior faculty, I continued to work on this topic, but started to connect recombination directly with human diseases, especially cancer, for the critical roles of homologous recombination in genome instability and DNA damage repair. Through exploration of the literature, I came to know the new anti-cancer strategy of synthetic lethality. Based on this study, I applied for a grant on computational methods to understand and predict new SL gene pairs as potential cancer drug targets, and got awarded by the Ministry of Education, Singapore. This paper is part of this project.

What was previously known about the topic of your article?
There are several studies working on computational prediction for SL pairs. However, most of them focused on using individual features or single machine learning models. For example, Li et al. used protein domain as the main type of features and support vector machine (SVM) for SL prediction (Ref. [12] in the main text).

How has your work in this area advanced understanding of the topic?
Our work can shed light on both computational and biological aspects of SL prediction. Firstly, meta-analysis methods have been shown to improve the prediction accuracy by data integration and model combination. Secondly, we observed that similarity based features (e.g. relation between two proteins) are more important than lethality based features (e.g., characteristics for individual proteins). Thirdly, study of sig¬nalling pathways will be promising to understand and inter¬pret the underlying mechanisms of SL, as our manually collected SL pairs tend to occur in the same pathways.

What do you regard as being the most important aspect of the results reported in the article?
By comparing three types of human SL pairs (as shown in Table 6 in the main text of our article), our manually collected SL pairs are more likely to be involved in the same pathways than those predicted from yeast SL pairs. These results indicate that we may derive more features from signaling pathways for SL prediction. Our next step is to study the topological and dynamic properties of signaling pathways (e.g. crosstalk) to further improve the prediction of SL gene pairs.

http://www.ntu.edu.sg/home/zhengjie/

Friday, January 16, 2015

Published This Week (12th Jan - 16th Jan)

We are pleased to announce the publication of the following peer reviewed papers. Sign up to receive email alerts to receive immediate notification of new papers.

Biomarker Insights
Prednisolone-Induced Predisposition to Femoral Head Separation and the Accompanying Plasma Protein Changes in Chickens

Breast Cancer: Basic and Clinical Research
An Interesting Pathological Diagnosis - Adenoid Cystic Carcinoma in an Adolescent Girl

Cancer Informatics
Network-Constrained Group Lasso for High-Dimensional Multinomial Classification with Application to Cancer Subtype Prediction

Practical Issues in Screening and Variable Selection in Genome-Wide Association Analysis

Clinical Medicine Insights: Case Reports
A Case of Successful Laparoscopic Surgery for Tubal Stump Pregnancy After Tubectomy

Skin Squamous Cell Carcinoma Presenting as Cellulitis

Clinical Medicine Insights: Gastroenterology
Surgical Management of Adenocarcinoma of the Pancreatic Uncinate Process in a Cancer Hospital in Egypt

Clinical Medicine Insights: Pediatrics
Hepatic Dysfunction in Asphyxiated Neonates: Prospective Case-Controlled Study

A Case of Hydrometrocolpos and Polydactyly

Clinical Medicine Reviews in Therapeutics
Safety and Efficacy of Buprenorphine Patch in the Management of Chronic Pain

Evolutionary Bioinformatics
Correction to: "In Silico Detection of Virulence Gene Homologues in the Human Pathogen Sphingomonas Spp."

Glycobiology Insights
Role of Galectin-3 in Cancer Metastasis

Monday, January 12, 2015

Interview with Author Dr David Johnson

This author interview is by Dr David Johnson, of Imperial College London.  Dr Johnson's full paper, Semantically Linking In Silico Cancer Models, is available for download in Cancer Informatics.

Please summarise for readers the content of your article.

Our paper describes a new approach to thinking about the informatics behind cancer models. We think of computational models as any other data, which can be linked to metadata. We use connected property graphs as a means to representing data in such a way that meaningful questions can be asked of a database containing many cancer models. Models can be composed into larger models, even where different research groups have developed them. What our property-graph approach enables is a way of exploring possible model combinations based on semantic links, primarily through computaitonal interfaces, where compatibilities may be reasoned based on common units, computaional types, and biological concepts. The actual composition of models would still require a lot of rework and validation. In our paper we show two examples of describing cancer models as property graphs: one based on an EGFR-ERK pathway module, the other on a decomposed vascular tumour growth modelling framework.

How did you come to be involved in your area of study?

I have worked on life science and biological informatics since beginning my postdoctoral research, initially working on developing software for phylogenetics (the study of evolutionary relationships among populations and species) research in Professor Mark Pagel's Evolutionary Biology Group at the Univeresity of Reading, UK. Following this, I was appointed to the University of Oxford's Computing Laboratory (now called the Department of Computer Science) to work on the ‘Transatlantic Tumor Model Repositories' project developing interoperable databases between the US and Europe. This body of work eventually led to the work described in our contributions in this paper.

What was previously known about the topic of your article?

The idea of using linked data is not novel - in fact in biology in general, relating data and models to domain knowledge is commonplace, where there is a mature ecosytem of biological standards and ontologies to manage the diversity of data in biomedical sciences. There are established Web standards, such as RDF, OWL and SPARQL, are used to link datasets together. However these technologies primary purpose is to enable interoperation across distributed systems on the Web. Our approach is to link data in the first instance, within a cancer model database.

How has your work in this area advanced understanding of the topic?

Biological data management is creating new use cases for ‘NoSQL' databases including those that adopt the property graph data model, such as Neo4j that we used in our study. What we have proven is that linking model data, in particular model interfaces (input and output parameters) has the potential to create a system by which we can explore cancer model compositions. The challenge now is to use property graphs to build up a comprehensive resource of cancer models linked to metadata, to hopefully have an environment by which we can discover new candidate model compositions that could steer multiscale model research.

What do you regard as being the most important aspect of the results reported in the article?

Linking cancer models to metadata is a first step to producing an ecosystem of models and data. What we envisage is that we could link datasets into our property graphs, where not only model compositions could be inferred, but data-model combinations that may have previously not been identified could be found. Our focus was very much on the data management aspect of cancer informatics that we hope will in-turn help further the science in cancer research.

If you would like to include a link to a departmental webpage, LinkedIn profile, or other webpage where readers can learn more about your work paste it below:

There is a live demo of some of the work presented in the paper available here: http://gist.neo4j.org/?6038a7b526bfa48da2c0

LinkedIn: http://uk.linkedin.com/in/drdavidjohnson

Twitter: @NuDataScientist

ORCiD: http://orcid.org/0000-0002-2323-6847

Friday, January 9, 2015

Published This Week (5th Jan - 9th Jan)

We are pleased to announce the publication of the following peer reviewed papers. Sign up to receive email alerts to receive immediate notification of new papers.

Cancer Informatics
Detection of Pancreatic Cancer Biomarkers Using Mass Spectrometry

Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders
Knee Osteoarthritis Injection Choices: Platelet-Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial)

Clinical Medicine Insights: Cardiology
Multi-Detector Coronary CT Imaging for the Identification of Coronary Artery Stenoses in a "Real-World" Population

Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction

Investigating Cardiac MRI Based Right Ventricular Contractility As A Novel Non-Invasive Metric of Pulmonary Arterial Pressure

Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation

Clinical Medicine Insights: Endocrinology and Diabetes
Combination of Linagliptin and Metformin for the Treatment of Patients with Type 2 Diabetes

Clinical Medicine Insights: Oncology
Cisplatin, Cetuximab, and Radiation in Locally Advanced Head and Neck Squamous Cell Cancer: A Retrospective Review

Clinical Medicine Insights: Pathology
Expression Distribution of Cancer Stem Cells, Epithelial to Mesenchymal Transition, and Telomerase Activity in Breast Cancer and Their Association with Clinicopathologic Characteristics

Environmental Health Insights
Sexual Harassment and Feeding Inhibition Between Two Invasive Dengue Vectors

Evolutionary Bioinformatics
Genome-Wide Characterization of miRNAs Involved in N Gene-Mediated Immunity in Response to Tobacco Mosaic Virus in Nicotiana benthamiana

International Journal of Tryptophan Research
Enantiomeric Separation of Monosubstituted Tryptophan Derivatives and Metabolites by HPLC with a Cinchona Alkaloid-Based Zwitterionic Chiral Stationary Phase and Its Application to the Evaluation of the Optical Purity of Synthesized 6-Chloro-L-Tryptophan

Japanese Clinical Medicine
A Case of Fetal Intestinal Volvulus Without Malrotation Causing Severe Anemia

Particle Physics Insights
Electroweak Radiative Corrections to h0 Production in Association with a Pair of Tau-sneutrino at e+ e- Linear Colliders

Wednesday, January 7, 2015

Public Science Insights: Nanotechnology and the organ donation shortage?

The world is facing a growing crisis as the number of patients on organ donation waiting lists far outpaces the number of adequate organs available for transplantation. Increased vital organ failure in the aging population of the West, twinned with rapidly improving post transplantation survival rates, have served to compound this issue. For example, in the US alone more than 120,000 people are currently on the transplant waiting list; on average 18 people die everyday while waiting for a transplant, and every 10 minutes another name is added to the list1.

An often cited solution to this growing problem is the promise of Tissue Engineering; the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. A basic schematic of a typical Tissue Engineering approach (Figure 1) sees cells isolated from a patients injured tissue and cultivated in the lab before being seeded on a specialised scaffold and re-implanted into the body. Tissue Engineering has received a lot of recent press due to the pioneering advances made by the likes of Robert Langer and Anthony Atala; the latter having successfully tissue engineered bladders and vaginal organs2. The key is to isolate undifferentiated cells, expand them to sufficient quantities and then use a scaffold to direct their differentiation into the cell type of choice. For example, in engineering a blood vessel you might isolate endothelial-progenitor cells to form the inner lining and mesenchymal stem cells for the outer connective tissue. You may then create a cylindrical scaffold that resembles a blood vessel and seed endothelial-progenitors on the inside and mesenchymal stem cells on the outside. If you had created a scaffold that resembled their normal biological environment closely enough, the cells may be ‘tricked' into forming a new section of blood vessel, which could be implanted into the patient.

Biologists and material scientists now know a great deal about the features of basic structures such as a blood vessel. We know that endothelial cells are more likely to be happy if seeded onto a very smooth surface and so this is how we would manufacture a tissue-engineered substitute. We also know that if endothelial cells are subjected to flow they will produce a factor known as VEGF, which promotes blood vessel formation, and so they may be cultured in a flow chamber. The tough connective tissue on the outside of the vessel, however, requires nanoscale ridges for differentiating fibroblasts to ‘hang on' to. By providing these biomimetic nanoscale features, successful tissue engineering becomes a step closer.

Cells exist in a nanoscale environment, and it is only by understanding and replicating the nanoscale features of their environment that we will be able to engineer very complex tissues, such as the solid organs. It may be a long way off, but there is a chance that new technologies such as those developed by Anthony Atala could solve the growing crisis in organ transplantation.

Figure 1 - Provided by the author

Schematic illustrating the typical stages involved in Tissue Engineering. First a tissue biopsy is taken from the patient. Cells of interest are isolated or derived according to literature best practices. Once bulked up, cells can be seeded onto a biomimetically-designed scaffold and cultured in a bioreactor designed to mimic the in vivo environment. The cell populated scaffold can then be grafted onto tissues of interest in the patient where they can help repair or augment organ function.

References
1. Department of Health and Human Services. U.S. Government Information on Organ and Tissue Donation and Transplantation. (2014). at
2. TEDMED. Growing new organs. (2009). at
3. Cassidy, J. W. Nanotechnology in the Regeneration of Complex Tissues. Bone Tissue Regen. Insights 25 (2014). doi:10.4137/BTRI.S12331

Dr John W Cassidy is author of the recently published paper Nanotechnology in the Regeneration of Complex Tissues, available for download now in Bone and Tissue Regeneration Insights

 

Monday, January 5, 2015

Published in December

We are pleased to announce the publication of the following peer reviewed papers.  Sign up to receive email alerts to receive immediate notification of new papers.


Air, Soil and Water Research
Biological Approach for Recycling Waste Water in Iraq

Bioinformatics & Biology Insights
POEAS: Automated Plant Phenomic Analysis Using Plant Ontology

Biomarkers in Cancer
Allele and Genotype Distributions of DNA Repair Gene Polymorphisms in South Indian Healthy Population

Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer

Biomarker Insights
Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

Cancer Growth and Metastasis
A Role for the Cavin-3/Matrix Metalloproteinase-9 Signaling Axis in the Regulation of PMA-Activated Human HT1080 Fibrosarcoma Cell Neoplastic Phenotype

Cancer Informatics
Bayesian Joint Selection of Genes and Pathways: Applications in Multiple Myeloma Genomics

Computational Construction of Antibody–Drug Conjugates Using Surface Lysines as the Antibody Conjugation Site and a Non-cleavable Linker

Semantically Linking In Silico Cancer Models

Normal Cell-Type Epigenetics and Breast Cancer Classification: A Case Study of Cell Mixture–Adjusted Analysis of DNA Methylation Data from Tumors

Growth Rate Analysis and Efficient Experimental Design for Tumor Xenograft Studies

Stratified Pathway Analysis to Identify Gene Sets Associated with Oral Contraceptive Use and Breast Cancer

CARAT-GxG: CUDA-Accelerated Regression Analysis Toolkit for Large-Scale Gene–Gene Interaction with GPU Computing System

Overcome Support Vector Machine Diagnosis Overfitting

Statistical Issues in the Design and Analysis of nCounter Projects

Web Tool for Estimating the Cancer Hazard Rates in Aging

FocalCall: An R Package for the Annotation of Focal Copy Number Aberrations

Supervised Classification by Filter Methods and Recursive Feature Elimination Predicts Risk of Radiotherapy-Related Fatigue in Patients with Prostate Cancer 

Health Information Technology in Oncology Practice: A Literature Review 

Revealing Biological Pathways Implicated in Lung Cancer from TCGA Gene Expression Data Using Gene Set Enrichment Analysis

Assessment of Subnetwork Detection Methods for Breast Cancer

Streamlined Genome Sequence Compression using Distributed Source Coding

Trial Prospector: Matching Patients with Cancer Research Studies Using an Automated and Scalable Approach

A Pan-Cancer Analysis of Alternative Splicing Events Reveals Novel Tumor-Associated Splice Variants of Matriptase

Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders
An 8-Week Knee Osteoarthritis Treatment Program of Hyaluronic Acid Injection, Deliberate Physical Rehabilitation, and Patient Education is Cost Effective at 2 Years Follow-up: The OsteoArthritis Centers of AmericaSM Experience

Clinical Medicine Insights: Cardiology
Endovascular Treatment of Aneurysms of the Popliteal Artery By a Covered Endoprosthesis

Antioxidant Beverages: Green Tea Intake and Coronary Artery Disease

Native T1 Mapping of the Heart – A Pictorial Review

Clinical Medicine Insights: Case Reports
Stiff Man Syndrome: A Diagnostic Dilemma in a Young Female with Diabetes Mellitus and Thyroiditis

Clinical Medicine Insights: Endocrinology and Diabetes
Plantar Pressure as a Risk Assessment Tool for Diabetic Foot Ulceration in Egyptian Patients with Diabetes 

Monitoring HIV-infected Patients with Diabetes: Hemoglobin A1c, Fructosamine, or Glucose?

Clinical Medicine Insights: Oncology
Clinicians' Expectations for Gene-Driven Cancer Therapy

The Use of Pharmacogenomics for Selection of Therapy in Non-Small-Cell Lung Cancer

Micro-cost Analysis of ALK Rearrangement Testing by FISH to Determine Eligibility for Crizotinib Therapy in NSCLC: Implications for Cost Effectiveness of Testing and Treatment

Changes in Protein Level in the Cerebrospinal Fluid of a Patient with Cerebral Radiation Necrosis Treated with Bevacizumab

Cancer-Associated Thrombosis: An Overview Oncology    

Clinical Medicine Insights: Women's Health
Creation and Validation of the Self-esteem/Self-image Female Sexuality (SESIFS) Questionnaire

Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction

Drug Target Insights
Genome-wide Analysis of Mycoplasma hominis for the Identification of Putative Therapeutic Targets

Environmental Health
Environmental Changes Can Produce Shifts in Chagas Disease Infection Risk

Kissing Bugs in the United States: Risk for Vector-Borne Disease in Humans

Potential Health Effects Associated with Dermal Exposure to Occupational Chemicals

An Evaluation of Welding Processes to Reduce Hexavalent Chromium Exposures and Reduce Costs by Using Better Welding Techniques 

Emergency Mosquito Control on a Selected Area in Eastern North Carolina After Hurricane Irene

Aedes aegypti and Aedes albopictus Habitat Preferences in South Texas, USA

Evolutionary Bioinformatics
Computational Analysis Reveals a Successive Adaptation of Multiple Inositol Polyphosphate Phosphatase 1 in Higher Organisms Through Evolution

SWAMP: Sliding Window Alignment Masker for PAML

Evaluating the Accuracy and Efficiency of Multiple Sequence Alignment Methods

In Silico Detection of Virulence Gene Homologues in the Human Pathogen Sphingomonas Spp.

Gene Regulation and Systems Biology
A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia

A Hypothetical Protein of Alteromonas macleodii AltDE1 (amad1_06475) Predicted to be a Cold-Shock Protein with RNA Chaperone Activity

International Journal of Insect Science
Effects of Delayed Mating and Access to Water on Oviposition and Longevity in Female Amyelois transitella

Activity of the Antioxidant Defense System in a Typical Bioinsecticide- and Synthetic Insecticide-treated Cowpea Storage Beetle Callosobrochus maculatus F. (Coleoptera: Chrysomelidae)

International Journal of Tryptophan Research
Mechanisms of the Pellagragenic Effect of Leucine: Stimulation of Hepatic Tryptophan Oxidation by Administration of Branched-Chain Amino Acids to Healthy Human Volunteers and the Role of Plasma Free Tryptophan and Total Kynurenines

Journal of Medical Education and Curricular Development
Progress Testing for Medical Students at The University of Auckland: Results from The First Year of Assessments

Magnetic Resonance Insights
Investigation of Fat Metabolism during Antiobesity Interventions by Magnetic Resonance Imaging and Spectroscopy

Rehabilitation Process and Outcome
Vision Rehabilitation in Patients with Age-related Macular Degeneration

Assessment of Quality of Life of People Who Stutter: A Cross-sectional Study

Signal Transduction Insights
Prion Protein Signaling in the Nervous System—A Review and Perspective

Translational Oncogenomics
Evidence for the Influence of the Iron Regulatory MHC Class I Molecule HFE on Tumor Progression in Experimental Models and Clinical Populations

Tuesday, December 30, 2014

New Journals Added to Pubmed

We are pleased to announce that four more Libertas Academica journals are now available on Pubmed.

These are;

             Clinical Medicine Insights: Blood Disorders

             Virology: Research and Treatment

             Open Journal of Cardiovascular Surgery

             Genetics and Epigenetics

Having our journals included in Pubmed means enhanced visibility for published papers and permanent archiving of papers in Pubmed Central in addition to our existing archiving arrangements with CLOCKSS and LOCKSS. It also means all newly published papers will be added to Pubmed within approximately ten days following publication.

The full list of all our journals, including the 48 listed on Pubmed, can be found on the Journal Home Page

Tuesday, December 23, 2014

Dr Tartakoff discusses Progression of Disease

This author interview is by Dr Alan Tartakoff, of Case Western Reserve University.  Dr Tartakoff's full paper, The Axis of Progression of Disease, is available for download in Cancer Informatics.

Please summarise for readers the content of your article.

We describe fundamental concerns that plague the analysis of disease.  The most crucial is the realization that outcomes of single genetic or environmental changes often are unpredicatable - given the large number of molecular interactions that occur.   Moreover, the degree of unpredictability is likely to increase with time of progression - in other words, as a function of the cumulative set of secondary and tertiary changes.  From this chronological perspective, it becomes evident that possible targets for intervention are those that lie at early points.  This is both because such targets should be easier to predict and because at early times fewer far-removed changes will have occurred.  This realization is sobering in the context of diseases of unknown or multiple causation.  If distinct initiating circumstances do lead to overlapping molecular phenotypes, those potential targets are likely to lie far downstream, i.e. after irreversible changes have occurred.  We therefore describe strategies that might be used to identify early changes.

As a fascinating example of the prevalence of secondary, seemingly-unrelated changes, studies of cells that carry single well-defined mutations show that they often acquire multiple secondary mutations.

How did you come to be involved in your area of study?

My fascination with chronology started with an interest in Huntington's Disease.  Although only a single gene is mutated, studies of Huntington's have led to the realization that even a single genetically well-defined mutation can have multiple unmanageable molecular consequences.   Huntington's investigators have concluded that major damage is characteristic of mitochondria, membrane traffic, and the mitotic spindle.  Durer had to deal with some of the same varied testimony in making his famous drawing of an elephant.

What was previously known about the topic of your article?

A great deal was known about genetic lesions and the ultimate deadly consequences to which they lead, both for cancer and for other diseases.  Nevertheless, causal connections have often been unclear and targets for possible molecular intervention have been difficult to identify.   The bioinformatic studies of my co-author (Di Wu) exemplify approaches that can be used to analyze such complexity.

How has your work in this area advanced understanding of the topic?

I hope that our insistence on the chronology of change will be beneficial to others.  Certainly, Di Wu's algorithms and correlative studies of large data sets will be helpful.

What do you regard as being the most important aspect of the results reported in the article?

The realization that we need to take into consideration the sequence of metabolic, biochemical and genetic changes that occur.  Focus on a single time-point will often not be sufficient.

Dr Tartakoff's Institution Profile

Published Recently (8th - 23rd December)

We are pleased to announce the publication of the following peer reviewed papers. Sign up to receive email alerts to receive immediate notification of new papers.

Bioinformatics & Biology Insights
POEAS: Automated Plant Phenomic Analysis Using Plant Ontology

Biomarker Insights
Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

Cancer Informatics
Statistical Issues in the Design and Analysis of nCounter Projects

Web Tool for Estimating the Cancer Hazard Rates in Aging

Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders
An 8-Week Knee Osteoarthritis Treatment Program of Hyaluronic Acid Injection, Deliberate Physical Rehabilitation, and Patient Education is Cost Effective at 2 Years Follow-up: The OsteoArthritis Centers of AmericaSM Experience

Clinical Medicine Insights: Cardiology
Endovascular Treatment of Aneurysms of the Popliteal Artery By a Covered Endoprosthesis

Antioxidant Beverages: Green Tea Intake and Coronary Artery Disease

Clinical Medicine Insights: Oncology
Clinicians' Expectations for Gene-Driven Cancer Therapy

Clinical Medicine Insights: Women's Health
Creation and Validation of the Self-esteem/Self-image Female Sexuality (SESIFS) Questionnaire

Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction

Environmental Health Insights
Potential Health Effects Associated with Dermal Exposure to Occupational Chemicals

An Evaluation of Welding Processes to Reduce Hexavalent Chromium Exposures and Reduce Costs by Using Better Welding Techniques

Evolutionary Bioinformatics
Computational Analysis Reveals a Successive Adaptation of Multiple Inositol Polyphosphate Phosphatase 1 in Higher Organisms Through Evolution

Gene Regulation and Systems Biology
A Hypothetical Protein of Alteromonas macleodii AltDE1 (amad1_06475) Predicted to be a Cold-Shock Protein with RNA Chaperone Activity

International Journal of Insect Science
Activity of the Antioxidant Defense System in a Typical Bioinsecticide- and Synthetic Insecticide-treated Cowpea Storage Beetle Callosobrochus maculatus F. (Coleoptera: Chrysomelidae)

Rehabilitation Process and Outcome
Vision Rehabilitation in Patients with Age-related Macular Degeneration

Assessment of Quality of Life of People Who Stutter: A Cross-sectional Study

 

Friday, December 19, 2014

Dr Friedenson on Breast Cancer Mutations

This author interview is by Dr Bernard Friedenson, of University of Illinois. Dr Friedenson's full paper, Many Breast Cancer Mutations Parallel Mutations in Known Viral Cancers, is available for download in Journal of Genomes and Exomes.

Please summarise for readers the content of your article
Infections play a larger role in breast and in other cancers than we previously thought. Gaps in immunity or in infection barriers caused by distinct individual sets of gene mutations make cancer cells more susceptible than normal cells to infections that can exploit cancer mutations. The effect is different in different cancers and explains why it has been so difficult to pin down a specific virus as a cause of breast cancer. The findings can form the basis for a new generation of cancer therapy.

How did you come to be involved in your area of study?
My father died from cancer after a long and terrible struggle.

What was previously known about the topic of your article?
Cancer was thought to develop because of mutations in 2-8 driver genes, with >99.9% of mutations being irrelevant passengers. Immune deficiencies have long been associated with cancer but how this related to the 2-8 driver genes was never clear. The understanding was so poor that immune deficiency models were thought to be weak because people taking antibiotics still got cancer.

How has your work in this area advanced understanding of the topic?
Gaps in immunity or in infection barriers caused by distinct individual sets of mutations make cancer cells more susceptible than normal cells to infections that can exploit the mutations. Some branches of the immune system still function normally. Acquired deficits in immunity may be a lurking variable that explains why some studies find associations between cancer and a given viral infection while other studies do not. The work forms the basis of a new model for cancer based firmly on genomic evidence. Many mutations that were previously discarded as mere passengers in the cancer process actually set the stage for infections that can exploit the mutations. These infections may well cause cancer. The greater ease of infecting cancer cells may be used to specifically destroy them while leaving normal cells intact.

What do you regard as being the most important aspect of the results reported in the article?
In several examples thus far, genomic evidence can be used to suggest effective therapy and predict an individual patient's response. This may foretell new and more rational cancer therapy.

Dr Friedenson's Linked In profile

Friday, December 12, 2014

Published This Week (8th Dec - 12th Dec)

Kissing Bugs in the United States: Risk for Vector-Borne Disease in HumansWe are pleased to announce the publication of the following peer reviewed papers. Sign up to receive email alerts to receive immediate notification of new papers.

Air, Soil and Water Research
Biological Approach for Recycling Waste Water in Iraq

Biomarkers in Cancer
Allele and Genotype Distributions of DNA Repair Gene Polymorphisms in South Indian Healthy Population

Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer

Cancer Growth and Metastasis
A Role for the Cavin-3/Matrix Metalloproteinase-9 Signaling Axis in the Regulation of PMA-Activated Human HT1080 Fibrosarcoma Cell Neoplastic Phenotype

Cancer Informatics
Bayesian Joint Selection of Genes and Pathways: Applications in Multiple Myeloma Genomics

Computational Construction of Antibody-Drug Conjugates Using Surface Lysines as the Antibody Conjugation Site and a Non-cleavable Linker

Semantically Linking In Silico Cancer Models

Normal Cell-Type Epigenetics and Breast Cancer Classification: A Case Study of Cell Mixture-Adjusted Analysis of DNA Methylation Data from Tumors

Growth Rate Analysis and Efficient Experimental Design for Tumor Xenograft Studies

Stratified Pathway Analysis to Identify Gene Sets Associated with Oral Contraceptive Use and Breast Cancer

CARAT-GxG: CUDA-Accelerated Regression Analysis Toolkit for Large-Scale Gene-Gene Interaction with GPU Computing System

Overcome Support Vector Machine Diagnosis Overfitting

Clinical Medicine Insights: Oncology
The Use of Pharmacogenomics for Selection of Therapy in Non-Small-Cell Lung Cancer

Micro-cost Analysis of ALK Rearrangement Testing by FISH to Determine Eligibility for Crizotinib Therapy in NSCLC: Implications for Cost Effectiveness of Testing and Treatment

Changes in Protein Level in the Cerebrospinal Fluid of a Patient with Cerebral Radiation Necrosis Treated with Bevacizumab

Drug Target Insights
Genome-wide Analysis of Mycoplasma hominis for the Identification of Putative Therapeutic Targets

Environmental Health
Environmental Changes Can Produce Shifts in Chagas Disease Infection Risk

Kissing Bugs in the United States: Risk for Vector-Borne Disease in Humans

Evolutionary Bioinformatics
Evaluating the Accuracy and Efficiency of Multiple Sequence Alignment Methods

In Silico Detection of Virulence Gene Homologues in the Human Pathogen Sphingomonas Spp.

Gene Regulation and Systems Biology
A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia

International Journal of Insect Science
Effects of Delayed Mating and Access to Water on Oviposition and Longevity in Female Amyelois transitella

Tuesday, December 9, 2014

Public Science Insights article on the life history calendar and how can it be used to understand drug use and treatment

Addiction and public health researchers endeavor to understand the complex relationship between life events and substance using behaviors to better disentangle their interaction with access to health services and treatment outcomes.  Typically, this research relies on standardized questionnaires, which tend to overlook detailed lifetime experiences. Qualitative methods are one solution that allow for a more in-depth collection of individual experiences. However beneficial, these methods are more resource intensive than quantitative methods. Thus, obtaining a comprehensive picture of a person's patterns of drug use and treatment access poses methodological challenges to the public health researcher.  

Life event calendars and timelines are alternative methods used in health or social surveys that may provide the researcher with a feasible and efficient means for measuring detailed life events and their relationship with participant behavours, such as patterns of substance use, addiction treatment access and outcomes.  The life history calendar (LHC) is one example of a calendar and timeline instrument. This tool collects information on lifetime events and is used to identify the occurrence, timing, sequence and duration of events over the life course. 

The LHC has shown to improve the quality and completeness of the reported retrospective data.  A typical LHC uses a graphical display; the vertical axis shows the participant's life course or reference period of interest and the events are labeled on the horizontal axis. This graphical display facilitates memory recall of the timing and sequence of life events and is particularly useful for recalling less salient or more frequent events. The graphical display also allows interviewers to identify gaps in reported data. The accuracy of data is therefore greatly improved.

The LHC has been applied in the field of addictions, primarily to collect daily patterns of substance use, typically with a one-month follow-back time period. In addition, other studies have included questions in the LHC regarding substance use as one of the factors that could explain the health or social outcome of interest.  In our recent cross-sectional study among long-term opioid dependent (e.g., heroin) individuals, we used the LHC to strengthen quantitative data and to determine the relationship between life events (e.g., incarcerations, illnesses) with patterns of drug use and access to addiction treatment. Salient life events, such as the birth of a child, were used as reference points for recalling details surrounding drug use and treatment access. We were also able to determine transitions in the frequency and intensity of drug use and their relationship with life events and access to addiction treatment.

The primary challenge encountered was the use of a lifetime reference period for a large number of life events. To complete the LHC with accuracy and completeness, we emphasized the importance of the interviewer's role and training, as well as the use of complementary questionnaires. These questionnaires were used to refine the number of relevant life events.  Despite these challenges, detailed histories were collected and allowed us to uncover important time sensitive data on the relationship between events over the life course with patterns of substance use and access to addiction treatment. This data can explain relationships between these complex lifetime events otherwise not captured with questionnaires. Uncovering such complex relationships has the potential to improve addiction treatment outcomes in a number of capacities, and could be used for example, to inform timely interventions and to prevent relapses.

Kirsten Marchand, Heather Palis, Jill Fikowski, Eugenia Oviedo-Joekes are the authors of the recently published paper, Feasibility of Applying the Life History Calendar in a Population of Chronic Opioid Users to Identify Patterns of Drug Use and Addiction Treatment, available for download now in Substance Abuse: Research and Treatment

Friday, December 5, 2014

Published This Week (1st December - 5th December)

We are pleased to announce the publication of the following peer reviewed papers. Sign up to receive email alerts to receive immediate notification of new papers.

Cancer Informatics
FocalCall: An R Package for the Annotation of Focal Copy Number Aberrations

Supervised Classification by Filter Methods and Recursive Feature Elimination Predicts Risk of Radiotherapy-Related Fatigue in Patients with Prostate Cancer

Health Information Technology in Oncology Practice: A Literature Review

Revealing Biological Pathways Implicated in Lung Cancer from TCGA Gene Expression Data Using Gene Set Enrichment Analysis

Assessment of Subnetwork Detection Methods for Breast Cancer

Streamlined Genome Sequence Compression using Distributed Source Coding

Trial Prospector: Matching Patients with Cancer Research Studies Using an Automated and Scalable Approach

A Pan-Cancer Analysis of Alternative Splicing Events Reveals Novel Tumor-Associated Splice Variants of Matriptase


Clinical Medicine Insights: Cardiology

Native T1 Mapping of the Heart - A Pictorial Review

Clinical Medicine Insights: Case Reports
Stiff Man Syndrome: A Diagnostic Dilemma in a Young Female with Diabetes Mellitus and Thyroiditis

Clinical Medicine Insights: Endocrinology and Diabetes
Plantar Pressure as a Risk Assessment Tool for Diabetic Foot Ulceration in Egyptian Patients with Diabetes

Monitoring HIV-infected Patients with Diabetes: Hemoglobin A1c, Fructosamine, or Glucose?

Clinical Medicine Insights: Oncology

Cancer-Associated Thrombosis: An Overview Oncology

 

Environmental Health Insights
Emergency Mosquito Control on a Selected Area in Eastern North Carolina After Hurricane Irene

Aedes aegypti and Aedes albopictus Habitat Preferences in South Texas, USA

Evolutionary Bioinformatics
SWAMP: Sliding Window Alignment Masker for PAML

International Journal of Tryptophan Research
Mechanisms of the Pellagragenic Effect of Leucine: Stimulation of Hepatic Tryptophan Oxidation by Administration of Branched-Chain Amino Acids to Healthy Human Volunteers and the Role of Plasma Free Tryptophan and Total Kynurenines

Journal of Medical Education and Curricular Development
Progress Testing for Medical Students at The University of Auckland: Results from The First Year of Assessments

Magnetic Resonance Insights
Investigation of Fat Metabolism during Antiobesity Interventions by Magnetic Resonance Imaging and Spectroscopy

Signal Transduction Insights
Prion Protein Signaling in the Nervous System-A Review and Perspective

Translational Oncogenomics

Evidence for the Influence of the Iron Regulatory MHC Class I Molecule HFE on Tumor Progression in Experimental Models and Clinical Populations

Tuesday, December 2, 2014

Interview with Dr Serena Delbue and Dr Pasquale Ferrante

This author interview is by Dr Serena Delbue and Dr Pasquale Ferrante, of the Department of Biomedical, Surgical and Dental Sciences, University of Milano, Milano, Italy. Their full paper, A Potential Linkage Between the JC and BK Polyomaviruses and Brain and Urinary Tract Tumors: A Review of the Literature, is available for download in Advances in Tumor Virology

First please summarise for readers the content of your article.

The potential association between infectious agents and human tumors is very relevant, since worldwide about 16.1% of cancers are related to the presence of bacteria and/or viruses. We focused our attention on the polyomaviruses, that are small DNA viruses, establishing latency in the human host. The name polyomavirus derived from the Greek roots poly-, which means "many", and -oma, which means "tumours". These viruses were originally isolated in mouse (mPyV) and in monkey (SV40). In 1971 the first human polyomaviruses BK and JC were isolated and subsequently demonstrated to be ubiquitous in the human population. JCV and BKV usually infect the human population during early childhood and primary infection is often asymptomatic. These viruses can remain latent in the kidney cells of the host until reactivation which occurs during immunodepression. JCV causes progressive multifocal leukoencephalopathy (PML) in cases of severe immunodeficiency, generally due to HIV infection, whereas BKV causes nephropathy in patients who have undergone to kidney transplants.

PyVs are also able to induce cell transformation when they infect non-permissive cells where viral replication is not supported; this is in contrast to permissive cells, where the virus can replicate. It has been demonstrated by several in vitro studies that the main factor implicated in cell transformation and tumour development is the early protein LTAg, a multifunctional protein, fundamental for the viral life cycle of polyomaviruses, because it regulates the viral genome replication and gene expression. Because of this, JCV and BKV are considered good candidates for playing a role in the pathogenesis of human tumors.

Consequently, it is not surprising that JCV DNA and BKV DNA has been identified mainly in central nervous system tumors (JCV) and urothelial carcinomas of the renal pelvis, prostate, and bladder as well as renal cell carcinomas (BKV).

In this paper we reviewed the published literature and we described the potential association between JCV and BKV with brain and urinary tract tumors, respectively.

How did you come to be involved in your area of study?

We have been studying JCV and BKV since twenty years ago, and we are interested in the different pathogenic manifestations of their infection in the human population. Our previous studies have provided evidences that JCV genome and proteins could be found in the brain tumoral tissues, and that BKV genome could be found in prostate cancer tissues. However, the significance of these findings is still under debate and the topic deserves in depth-analysis, starting from the detailed study of the published literature on the potential association between human polyomaviruses and different forms of malignancies.

What was previously known about the topic of your article?

The question related to the involvement of viral infections in the development of human tumors is still very controversial. This is due to the fact that the majority of the studies did not provide a definitive and proven association between the virus presence, the transforming mechanism and the cancer onset and/or progression. Consequently, even if a large body of data and results are widely diffused in literature, the knowledge on the viral etiology of the tumors is incomplete.

How has your work in this area advanced understanding of the topic?

Our work summarized and tried to critically analyse all the results that have been so far published regarding the presence and the expression of the genome of JCV and BKV in the clinical specimens collected from patients with CNS and urinary tract tumors, respectively. Our intent was to provide a starting point for further epidemiological studies, given the important role of the viral infections as risk factors for the tumor development in humans.

What do you regard as being the most important aspect of the results reported in the article?

Although a role for JCV and BKV in malignant transformation was proposed more than 40 years ago, and although in vitro studies supported the oncogenic properties of the T Ag protein, there is still insufficient evidence of a casual association between these human PyVs and solid cancer development. To settle this issue, JCV and BKV should fulfill criteria that have been fixed for establishing a causal relationship between a virus and a tumor. These criteria include the detection of the viral genome and/or proteins in cancerous tissues, proven molecular mechanisms for inducing tumorigenesis and consistency of association. So far, there are many doubts regarding the fulfillment of the first and the third criteria. However, despite the "inadequate evidence of carcinogenicity in humans", the WHO International Agency for Cancer Research Monograph Working Group decided to classify JCV and BKV as "possibly carcinogenic to humans", belonging to group 2B, on the basis of the "sufficient evidence in experimental animals". Therefore, only further solid, clear-cut epidemiologic, histopathologic and DNA evidence will ultimately settle this urgent issue and will help to answer the still unsolved question: "Do JCV and BKV cause tumors in the human population?" When a complete understanding is reached, a vaccination approach for the prevention of polyomavirus infection may be proposed.

Monday, December 1, 2014

Published During November

We are pleased to announce the publication of the following peer reviewed papers.  Sign up to receive email alerts to receive immediate notification of new papers.

Analytical Chemistry Insights

A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method

Biochemistry Insights

Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma

Bone and Tissue Regeneration Insights

Nanotechnology in the Regeneration of Complex Tissues 

Cancer Informatics

Conducting Retrospective Ontological Clinical Trials in ICD-9-CM in the Age of ICD-10-CM

Type I Error Control for Tree Classification

A Bayesian Framework to Improve MicroRNA Target Prediction by Incorporating External Information

Clinical Medicine Insights: Cardiology

Stroke Awareness in Luxemburg: Deficit Concerning Symptoms and Risk Factors

Atherosclerosis As a Possible Extrahepatic Manifestation of Chronic Hepatitis C Virus Infection

Transcatheter Aortic Valve Implantation (TAVI): Is it Time for This Intervention to be applied in a Lower Risk Population?

Clinical Medicine Insights: Case Reports

Acute Iodine Toxicity From a Suspected Oral Methamphetamine Ingestion

Switching from Nitrate Therapy to Ranolazine in Patients with Coronary Artery Disease Receiving Phosphodiesterase Type-5 Inhibitors for Erectile Dysfunction 

A Case of Fallopian Tube Adenofibroma: Difficulties Associated with Differentiation from Ectopic Pregnancy

Clinical Medicine Insights: Oncology

Phase II Clinical Trial of Gefitinib for the Treatment of Chemonaïve Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status 

Clinical Medicine Insights: Trauma and Intensive Medicine

The Management of Pediatric Polytrauma: Review  

Complex Tibial Fractures: Tips and Tricks for Intramedullary Nail Fixation

Environmental Health Insights

Magnetic Resonance Imaging of Graded Skeletal Muscle Injury in Live Rats 

Generation of Reactive Oxygen Species from Silicon Nanowires 

Temporal and Spatial Distribution of Tick-Borne Disease Cases among Humans and Canines in Illinois (2000–2009)

Potential Contribution of Work-Related Psychosocial Stress to the Development of Cardiovascular Disease and Type II Diabetes: A Brief Review

Drug Target Insights

The Expression of Serum Antibodies Against Gonadotropin-releasing Hormone (GnRH1), Progonadoliberin-2, Luteinizing Hormone (LH), and Related Receptors in Patients with Gastrointestinal Dysfunction or Diabetes Mellitus

Health Services Insights

The Lebanese Society of Cardiology: Plans and Perspectives, Navigating Against Contrary Winds and Progressing Against All Odds 

Immunology and Immunogenetics Insights

Cellular Responses to Cytosolic Double-stranded RNA—The Role of the Inflammasome

Journal of Medical Education and Curricular Development

A Pilot Study on the Use of Lecture Tools to Enhance the Teaching of Pharmacokinetics and Pharmacodynamics 

Lymphoma and Chronic Lymphocytic Leukemias

The Role of Functional Imaging in Lymphoma: Current Controversies and Future Directions

Magnetic Resonance Insights

Damage to the Optic Chiasm in Myelin Oligodendrocyte Glycoprotein–Experimental Autoimmune Encephalomyelitis Mice

Microbiology Insights

Evaluative Profiling of Arsenic Sensing and Regulatory Systems in the Human Microbiome Project Genomes

Genetic Diversity and Allelic Frequency of Glutamate-Rich Protein (GLURP) in Plasmodium falciparum Isolates from Sub-Saharan Africa