Assessing the effects of symmetry on motif disovery and modeling

BACKGROUND: Identifying the DNA binding sites for transcription factors is a key task in modeling the gene regulatory network of a cell. Predicting DNA binding sites computationally suffers from high false positives and false negatives due to various contributing factors, including the inaccurate models for transcription factor specificity. One source of inaccuracy in the specificity models is the assumption of asymmetry for symmetric models. METHODOLOGY/PRINCIPAL FINDINGS: Using simulation studies, so that the correct binding site model is known and various parameters of the process can be systematically controlled, we test different motif finding algorithms on both symmetric and asymmetric binding site data. We show that if the true binding site is asymmetric the results are unambiguous and the asymmetric model is clearly superior to the symmetric model. But if the true binding specificity is symmetric commonly used methods can infer, incorrectly, that the motif is asymmetric. The resulting inaccurate motifs lead to lower sensitivity and specificity than would the correct, symmetric models. We also show how the correct model can be obtained by the use of appropriate measures of statistical significance. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the most commonly used motif-finding approaches usually model symmetric motifs incorrectly, which leads to higher than necessary false prediction errors. It also demonstrates how alternative motif-finding methods can correct the problem, providing more accurate motif models and reducing the errors. Furthermore, it provides criteria for determining whether a symmetric or asymmetric model is the most appropriate for any experimental dataset

Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers.

In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE) tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs), muscle invasive disease (MIBCs), and bladder cancer metastases (METs). We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic

May the black god stand please! : Biko's challenge to religion

Papers presented at the Forum for Religious Dialogue Symposium of the Research Institute for Theology and Religion held at the University of South Africa, Pretoria, 23-24 August 2008Research Institute for Theology and Religio

Beyond Traditional Ethics when Developing Assistive Technology for and with Deaf People in Developing Regions

There are limitations to traditional ethical approaches and procedures when engaged in assistive technology (AT) research for Deaf people in a developing region. Non-traditional issues arise as a consequence of employing action research, including but not limited to how informed consent is construed and obtained; empowerment of participants to become involved in co-design; awareness of unfamiliar cultural issues of participants (as opposed to subjects); and accommodating community-centred, as opposed to person-centred, nuances. This chapter describes AT research with an entity called Deaf Community of Cape Town (DCCT), a disabled people’s organisation (DPO) that works on behalf of a marginalised community of under-educated, under-employed and semi-literate Deaf people across metropolitan Cape Town. We describe how non-traditional ethical concerns arose in our experience. We reflect on how these ethical issues affect AT design, based on long-term engagement; and summarise the themes, what we have learned and how we modified our practise, and finally, offer suggestions to others working on AT in developing regions.Telkom, Cisco, Aria Technologies, THRIP, NRF, SANPADWeb of Scienc