Integrative Genomic Data Mining for Discovery of Potential Blood-Borne Biomarkers for Early Diagnosis of Cancer

Background: With the arrival of the postgenomic era, there is increasing interest in the discovery of biomarkers for the accurate diagnosis, prognosis, and early detection of cancer. Blood-borne cancer markers are favored by clinicians, because blood samples can be obtained and analyzed with relative ease. We have used a combined mining strategy based on an integrated cancer microarray platform, Oncomine, and the biomarker module of the Ingenuity Pathways Analysis (IPA) program to identify potential blood-based markers for six common human cancer types. Methodology/Principal Findings: In the Oncomine platform, the genes overexpressed in cancer tissues relative to their corresponding normal tissues were filtered by Gene Ontology keywords, with the extracellular environment stipulated and a corrected Q value (false discovery rate) cut-off implemented. The identified genes were imported to the IPA biomarker module to separate out those genes encoding putative secreted or cell-surface proteins as blood-borne (blood/serum/plasma) cancer markers. The filtered potential indicators were ranked and prioritized according to normalized absolute Student t values. The retrieval of numerous marker genes that are already clinically useful or under active investigation confirmed the effectiveness of our mining strategy. To identify the biomarkers that are unique for each cancer type, the upregulated marker genes that are in common between each two tumor types across the six human tumors were also analyzed by the IPA biomarker comparison function. Conclusion/Significance: The upregulated marker genes shared among the six cancer types may serve as a molecular tool to complement histopathologic examination, and the combination of the commonly upregulated and unique biomarkers may serve as differentiating markers for a specific cancer. This approach will be increasingly useful to discover diagnostic signatures as the mass of microarray data continues to grow in the ‘omics’ era

Large-scale integration of cancer microarray data identifies a robust common cancer signature

<p>Abstract</p> <p>Background</p> <p>There is a continuing need to develop molecular diagnostic tools which complement histopathologic examination to increase the accuracy of cancer diagnosis. DNA microarrays provide a means for measuring gene expression signatures which can then be used as components of genomic-based diagnostic tests to determine the presence of cancer.</p> <p>Results</p> <p>In this study, we collect and integrate ~ 1500 microarray gene expression profiles from 26 published cancer data sets across 21 major human cancer types. We then apply a statistical method, referred to as the <it>T</it>op-<it>S</it>coring <it>P</it>air of <it>G</it>roups (TSPG) classifier, and a repeated random sampling strategy to the integrated training data sets and identify a common cancer signature consisting of 46 genes. These 46 genes are naturally divided into two distinct groups; those in one group are typically expressed less than those in the other group for cancer tissues. Given a new expression profile, the classifier discriminates cancer from normal tissues by ranking the expression values of the 46 genes in the cancer signature and comparing the average ranks of the two groups. This signature is then validated by applying this decision rule to independent test data.</p> <p>Conclusion</p> <p>By combining the TSPG method and repeated random sampling, a robust common cancer signature has been identified from large-scale microarray data integration. Upon further validation, this signature may be useful as a robust and objective diagnostic test for cancer.</p

Chlamydia trachomatis Incidence and Re-Infection among Young Women – Behavioural and Microbiological Characteristics

This study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women.1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR.There were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (p<0.01) and for prevalent than re-infections (p<0.01).Chlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia

Cephalopods in neuroscience: regulations, research and the 3Rs

Cephalopods have been utilised in neurosci- ence research for more than 100 years particularly because of their phenotypic plasticity, complex and centralised nervous system, tractability for studies of learning and cellular mechanisms of memory (e.g. long-term potentia- tion) and anatomical features facilitating physiological studies (e.g. squid giant axon and synapse). On 1 January 2013, research using any of the about 700 extant species of ‘‘live cephalopods’’ became regulated within the European Union by Directive 2010/63/EU on the ‘‘Protection of Animals used for Scientific Purposes’’, giving cephalopods the same EU legal protection as previously afforded only to vertebrates. The Directive has a number of implications, particularly for neuroscience research. These include: (1) projects will need justification, authorisation from local competent authorities, and be subject to review including a harm-benefit assessment and adherence to the 3Rs princi- ples (Replacement, Refinement and Reduction). (2) To support project evaluation and compliance with the new EU law, guidelines specific to cephalopods will need to be developed, covering capture, transport, handling, housing, care, maintenance, health monitoring, humane anaesthesia, analgesia and euthanasia. (3) Objective criteria need to be developed to identify signs of pain, suffering, distress and lasting harm particularly in the context of their induction by an experimental procedure. Despite diversity of views existing on some of these topics, this paper reviews the above topics and describes the approaches being taken by the cephalopod research community (represented by the authorship) to produce ‘‘guidelines’’ and the potential contribution of neuroscience research to cephalopod welfare