Applied Bimatics - An Informatics & eHealth Blog

I am a clinician with a passion for informatics. This blog is about my eHealth journey exploring interoperability in Electronic Medical Records (EMR/EHR), Patient Safety, Pharmacovigilance, Data Analytics, Clinical Research and Bioinformatics in a clinical context. Comparing Canadian, Indian and Middle Eastern healthcare systems and services. Join our open facebook group here: https://www.facebook.com/groups/clinical.bioinformaticians/


Plasmin

Plasmin
Proteinases play an important role in conditions associated with inflammatory desquamation of the skin like psoriasis, atopic dermatitis and netherton syndrome. Proteinase inhibitors keep their activity under check. Today I read an article [1] about such an inhibitor called LEKTI (lympho-epithelial Kazal-type-related inhibitor) and the corresponding gene SPINK5, mutations of which is responsible for Netherton syndrome. Authors found that domain 6 and domain 15 inhibit 2 key serine proteinases called hK5 and hK7. They also found that domain 15 with 3 disulphide bonds (and not domain 6) also inhibit plasmin. Plasmin is important in the pathogenesis of pemphigus vulgaris which basically is an autoimmune disease [2]. Hence LEKTI domain 15 may be useful in the treatment of pemphigus vulgaris too. The relevance of the fact that drugs with sulfhydryl groups induce pemphigus with respect to the above finding can be explored.
Interested in further exploring LEKTI bioinformatically?
References:
  1. T. Egelrud et al. hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6. British Journal of Dermatology 2005;153:1200-1203.

  2. Naito K, Morioka S, Nakajima S, Ogawa H. Proteinase inhibitors block formation of pemphigus acantholysis in experiments models of neonatal mice and skin explants: effects of synthetic and plasma proteinase inhibitors on pemphigus acantholysis. J Invest Dermatol 1989; 93: 173-7.

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DSG3 BJD 2006 Jan 15

DSG3 (BJD 2006 Jan 154 pp67-71)
I was always interested in doing some bioinformatics project on basement membrane zone molecules. Authors have studies various DSG3 SNPs and found two different haplotypes in UK and Indian pemphigus vulgaris patients. Authors have suggested further investigation of this gene.
Structure of GPCRs (PLoS Comp Biol Feb 2006 2(2) p 88-99
Feb 2006 PLOS Computational Biology journal has an interesting article about structure prediction of G Protein – Coupled Receptors. Authors have employed the new threading assembly refinement (TASSER) method to predict the structures for all 907 putative GPCRs out of which at least 820 is supposed to have correct folds. The structures are available for noncommercial use from the university website in my links database. It may be useful for my MC1R study too as GRK2 and 6 are GPCR kinases involved in MC1R signaling. Time to refine my protocol further.

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Toll-like receptors


Toll-like receptors.
Ref: - British Journal of Dermatology 2005 153, pp1105-1113
Today I read one interesting article titled “Induction of toll-like receptors by propionibacterium acnes”. Toll-like receptors (TLRs) are recently identified group of receptors with homologues in Drosiphila, important in immediate immunological response. 10 different types of TLRs have been identified which are trans-membrane proteins with a leucine-rich extracellular domain and a cytoplasmic domain, called the TIR domain, analogous to the fruit fly Toll protein. They bind to various bacterial antigens like peptidoglycans, Lipoarabinomannans or lipo polysaccharides. Inflammation in acne is due to induction of TLR-2 and TLR-4.
Is there any similarity with MHCs?
Any role in lepra reactions?
Interested in exploring further?

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UIMA SDK from IBM

UIMA SDK from IBM
Today I explored the UIMA SDK from IBM. It is a software system that analyses large volumes of unstructured information, discover, organize and deliver relevant knowledge. An example they have sited as an application of UIMA is to find potential drug interactions by processing millions of medical abstracts. I will try to explore its application in medical diagnostics and find out whether I can use it in some way for my virtual dermatologist I am working on. Probably it has some applications in bioinformatics too!

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Biomedical Research

In this months biopharm I read about the spiralling cost of biomedical research. New drug approvals have flattened out in recent years, particularly for new molecular entities. As far as man power is concerned, over the last few years there has been an unprecedented increase in the number of bioinformaticians and there is no dearth of lead molecules. However clinical research personal failed to catch up and manufacturers are under pressure to find out more efficient ways to develop medical products. I think very soon the initial phases of clinical studies may become computer simulations and the actual human studies will become more targeted.

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About Me

As a Dermatologist and Informatician my research mainly involves application of bioinformatics techniques and tools in dermatological conditions. However my research interests are varied and I have publications in areas ranging from artificial intelligence, sequence analysis, systems biology, ontology development, microarray analysis, immunology, computational biology and clinical dermatology. I am also interested in eHealth, Health Informatics and Health Policy.

Address

Bell Raj Eapen
Hamilton, ON
Canada