Applied Bimatics - A Bioinformatics Blog

Delayed-Type hypersensitivity to latex: Computational prediction of MHC class II epitopes on latex allergens

noreply@blogger.com (Bell) — Fri, 01 Aug 2008 10:20:00 +0000

This article was rejected by several journals. Hence I feel the concept is fundamentally wrong. I have posted the full article here. The referee comment from the last journal is also included.

The object of the study is laudable. However, the data presented here is too preliminary for publication.
Class II MHC molecules bind short peptides of 12 to 20 residues long. The concept of MHC binding to whole antigen is grossly not acceptable as given in Table 1.
Moreover, studies of this nature require experimental verification for publication.
It is strongly advised to look at MHCBN, MHCPEP and SYFPETHI for the type of peptides MHC molecules bind.
The design of the study should be narrowed down to a single antigen with overlapping peptides to multiple class 2 alleles for a reasonable argument.

Key words
Natural Rubber Latex, MHC Class II.

Abstract
Delayed type hypersensitivity to natural rubber latex is rare compared to IgE mediated immediate reactions. Binding of allergens to MHC Class II is a crucial step in the presentation of antigens to CD4+ T Cells responsible for delayed reactions. Computational prediction of MHC class II epitopes on thirteen known latex allergens using SMM-align method revealed strong binding with several alleles. This shows that latex allergens are capable of initiating delayed type hypersensitivity in susceptible individuals.

Background
Natural rubber latex (NRL) derived from the rubber tree (Hevea brasiliensis) is an important allergen causing mostly IgE mediated immediate reactions like urticaria, angioedema and asthma. [1] The existence of a true NRL induced delayed type hypersensitivity (type IV) is still debated. Delayed type hypersensitivity reactions are attributed to additives like thiurams and carbamates. [2] The coexistence of the type I and type IV patterns and entities like protein contact dermatitis [3] further complicate the issue. However incidence of true type IV hypersensitivities ranging from 1.2 to 6% has been reported following the introduction of an NRL containing patch test series. [4]

During the sensitization phase of contact hypersensitivity, epidermal Langerhans cells internalise the allergen, migrate to the regional lymph node and present the processed allergen bound to MHC Class II molecules to CD4 T cells. MHC Class II binding site consists of a groove open at both ends and several pockets binding peptides with 13 to 25 residues. [5] MHC molecules exhibit high degree of genetic variation which enables them to bind variety of peptides.

As IgE from latex-sensitive patients bind to several proteins, there is still no consensus on which latex proteins are antigenic. However information on thirteen officially accepted latex allergens designated serially from Hev b 1 to 13 is available from the online repository www.allergen.org and are summarized in Table 1. [6,[7]

We tried to computationally predict the MHC class II epitopes on these antigens using SMM-align method. SMM-align is a novel stabilization matrix alignment method based on scoring matrices that evaluate the contribution to binding of different residues in a peptide. [8] T cells are likely to recognize MHC binding peptides and initiate a cellular response. [9]

Methodology
The protein sequences of all thirteen allergens were downloaded from www.allergen.org and were added to a single file. This file was used for MHC Class II epitope prediction with the publicly available SMM-align server using default parameters. The server returns IC50 prediction scores (concentration of competing ligand which displaces 50% of the specific ligand) covering fourteen HLA DR alleles for each nanomer within the query peptide. Allergens with at least one nanomer with IC50 value less than fifty were considered as binders.

Results
Strong binding to one or more alleles was shown by all allergens except Hev b 5. Hev b 2 was the most promiscuous allergen binding several alleles. DRB1*0101 was the most commonly bound allele. Results are summarized in Table 1.

Discussion
NRL is an allergen causing mostly IgE mediated immediate type hypersensitivity. Though there have been significant advances in molecular biology of latex allergens, their ability to initiate delayed-type hypersensitivity has been subject to debate. Computational prediction of MHC class II binding regions on latex allergens adds credence to reports of type IV contact hypersensitivity to NRL. [4]

Prediction of MHC binding peptides is a commonly employed step in the identification of T cell epitopes. [9] MHC epitope related data is available from several databases like SYFPEITHI, [10] MHCBN [11] and IEDB [12]. Several algorithms like ARB [13] and SMM-align [8] are available for prediction of MHC class II binding peptides. Algorithms for scanning promiscuous peptides that can bind multiple MHC class II molecules are also available. [14] Promiscuous peptides are important for vaccine development and immunotherapy. [5] In our study Hev b 2 bound to six out of fourteen tested HLA DR alleles.

Conclusion
Most of the characterized latex allergens contain segments which can strongly bind MHC class II alleles and are capable of initiating delayed type hypersensitivity without a hapten in susceptible individuals. Certain promiscuous allergens like Hev b 2 bind to several MHC alleles making them ideal candidates for immunotherapy. [15] However computational prediction of MHC binding has limited accuracy and clinical validation is essential.

References

1 Reunala T et al.,. Latex allergy and skin. Curr Opin Allergy Clin Immunol 4: 397-401 (2004) [PMID: 15349039]
2 Miri S et al.,. Prevalence of type I allergy to natural rubber latex and type IV allergy to latex and rubber additives in operating room staff with glove-related symptoms. Allergy Asthma Proc 28: 557-63 (2007) [PMID: 18034975]
3 Doutre MS. Occupational contact urticaria and protein contact dermatitis. Eur J Dermatol 15: 419-24 (2005) [PMID: 16280292]
4 Sommer S et al.,. Type IV hypersensitivity reactions to natural rubber latex: results of a multicentre study. Br J Dermatol 146: 114-7 (2002) [PMID: 11841376]
5 Wang P et al.,. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLoS Comput Biol 4: e1000048 (2008) [PMID: 18389056]
6 Breiteneder H et al.,. Molecular and immunological characteristics of latex allergens. Int Arch Allergy Immunol 116: 83-92 (1998) [PMID: 9652300]
7 Wagner S et al.,. Hevea brasiliensis latex allergens: current panel and clinical relevance. Int Arch Allergy Immunol 136: 90-7 (2005) [PMID: 15627782]
8 Nielsen M et al.,. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method. BMC Bioinformatics 8: 238 (2007) [PMID: 17608956]
9 Sette A et al.,. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol 153: 5586-92 (1994) [PMID: 7527444]
10 Schuler MM et al.,. SYFPEITHI: database for searching and T-cell epitope prediction. Methods Mol Biol 409: 75-93 (2007) [PMID: 18449993]
11 Bhasin M et al.,. MHCBN: a comprehensive database of MHC binding and non-binding peptides. Bioinformatics 19: 665-6 (2003) [PMID: 12651731]
12 Peters B et al.,. The immune epitope database and analysis resource: from vision to blueprint. PLoS Biol 3: e91 (2005) [PMID: 15760272]
13 Bui HH et al.,. Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications. Immunogenetics 57: 304-14 (2005) [PMID: 15868141]
14 Zhang GL et al.,. MULTIPRED: a computational system for prediction of promiscuous HLA binding peptides. Nucleic Acids Res 33: W172-9 (2005) [PMID: 15980449]
15 Tabar AI et al.,. Specific immunotherapy with standardized latex extract versus placebo in latex-allergic patients. Int Arch Allergy Immunol 141: 369-76 (2006) [PMID: 16943675]

Protein-Protein Docking Problem.

noreply@blogger.com (Bell) — Fri, 11 Jan 2008 08:44:00 +0000

I am looking for a solution to the following problem. Any insight will be greatly appreciated.

A membrane receptor (A) has an extracellular domain (AE), transmembrane domain (AT) and intracellular domain (AI).

A bacteria (B) binds to (AE) leading to dimerization of (A) at (AT) and subsequent downstream signaling through (AI).

(A) has no known natural ligands.

(A) has one known inhibitor (I) binding to (AE)

The structure of (AE) bound to (I) is available from PDB.

How do we identify which protein in (B) binds to (AE).

The obvious solution is to dock all proteins with known structures in (B) to all known pockets in AE. Any better solutions?

The art of taking online help:

noreply@blogger.com (Bell) — Thu, 01 Nov 2007 18:22:00 +0000

I am not a big time researcher with lots of international experience. However I would like to make an attempt to suggest few guidelines for the young Indian bioinformatician, seeking online help for project or showcasing their profile online.

How to address a researcher online? Generally in research community, people are not bothered much about show of respect. Hence sir, respected sir, the most adorable etc can be translated to lack of confidence or to too much submissiveness. Hence it is appropriate to address anybody by the second name adding the appropriate title. Just using the first name is also OK. However title is often taken seriously and addressing a Dr/Prof as Mr is a cardinal sin even if you add a liberal dose of sir/almighty to that.

Career guidance is often done face to face or over the phone or through forums specifically dedicated for that. However before posting career guidance questions to forums search the forum for similar questions unless your profile is unique. Questions like I am going to finish my Kinder Garden What should I do next to become a successful bioinformatician is unlikely to fetch many answers. If you dont have enough time to search the forum, dont expect anybody else to send a personal two page letter to you.

The same applies to very broad, open ended questions. Questions like How is bioinformatics important for clinical medicine? is unlikely to get much attention. Be as specific as possible. Do not expect others to provide complete answers in a platter. Answers will be mostly very short, incomplete and often cryptic (because you may not know what the other person is talking about). Be ready to do some background research on the answer rather than asking for more information.

Posting your profile in online forums is also an art. Bioinformatics is a very broad field and employers look for certain specific skills which you may not always have. I often see sequence analysis, genomics, proteiomics, computer programming, PERL, RUBY, EMERALD, systems biology, drug designing, structural and molecular biology, talking, reading and sleeping in the skill set, everyone competing to make the complete list. In reality, no body can be a complete bioinformatician and it is better to showcase your core competency which needs to be substantiated by your projects or publications.

Please post your comments / criticisms / suggestions here.

Bioinformatics Projects

noreply@blogger.com (Bell) — Fri, 02 Mar 2007 12:34:00 +0000

I feel bioinformatics projects broadly fall into three categories.

Academic project as part of UG or PG course.
Professional projects for biotech/drug companies
Hobbyist/personal projects

When you do an academic project it is important to achieve a preset target within a limited time frame. Hence you have to adopt a bottom up approach wherein you know what your final result is going to be and work your way up. It is always better to keep it simple. You always have time to do more complicated things later on.

Professional projects also have a predefined goal. However it has a wider scope but often has the backing of a team. Funding is also available. This is what most of us aspire to do once we become full fledged professionals.

The third type of projects is for people who are not primarily bioinformaticians, but try to explore this nascent specialty, keeping their field as the initial entry point. They often try a top down approach and may not be always successful!

Let me suggest the following topics, categorized based on your area of expertise.

IT Prepare a database (organism, disease, or any other) and deploy it online
Microbiology Select an organism and do a comparative genomic study
Biochemistry Model a pathway using systems biology tools and discuss its clinical significance.
Pharmacology Docking studies and study of the targets of existing drugs.
Clinicians Expression profile study of any disease of interest.
Vet / Agri Functional genomic study of any chosen gene.

Counting conditional Occurrences using Prolog.

noreply@blogger.com (Bell) — Mon, 04 Sep 2006 06:49:00 +0000

Counting conditional occurrences using Prolog.

I wanted to implement the following rule in prolog for my IISA project.

If the percentage of coil region is greater than 20% the homologue detection algorithms may become unreliable. The coil module of IISA returns prolog database in the following format.

coil(105,a,0.000).
coil(109,g,0.001).
coil(110,l,0.004).
coil(111,l,0.014).
coil(112,v,0.055).
coil(113,g,0.055).
coil(114,s,0.371).
coil(115,e,0.416).
coil(116,k,0.860).
coil(117,v,0.955).
coil(118,t,0.998).
coil(119,m,0.999).
coil(120,q,0.999).
coil(121,n,0.999).

ie coil(position, aminoacid, probability of being part of coil).

I wanted to count the number of facts with the probability exceeding a cutoff value, say 0.7.

Though it is simple problem, I could not find any solution for this even after googling for few hours. Finally I found this code on the net.

%Code to count the number of proofs for a goal. Found on the net.
count_proof(Goal, N) :-
            flag(counter, Outer, 0),
            (   call(Goal),
                flag(counter, Inner, Inner+1),
                fail;
                flag(counter, Count, Outer),
                N = Count
            ).
Though it worked well (I have still not figured out how!) the code is SWI-Prolog specific and did not work in JLog prolog applet I use for IISA web interface.

Finally I learned about findall and bagof
But still it took some time to figure out how to use findall for my purpose because the description read findall (Var, Database, Array) and to use length(Array). Using coil (_,_,A) as database will count only the number of aminoacids and I didn’t know how to implement the condition A>0.7.
Finally somewhere I found the actual definition for findall (Var, Goal, Array) which solved my problem, though I wasted a whole day on this simple problem.

Here is the final code.

%The region is coil if the value is greater than threshold
coil_region(Cutoff, Val):-
                     coil(_,_,Val),
                     Val>Cutoff.

coil_percent(Region, Total, Percent):-
                     setting(coil,X),
                     findall(Val,coil_region(X,Val),R),
                     length(R,Region),
                     findall(C,coil(_,_,C),A),
                     length(A,Total),
                     Total>0,        %Avoid division by zero
                     Percent is (Region/Total) * 100,!.

coil_percent(0,0,0).

IISA Home Page.

Zostavax

noreply@blogger.com (Bell) — Sat, 15 Jul 2006 13:32:00 +0000

Merck recently gained approval for a vaccine called Zostavax for preventing herpes zoster reactivation in elderly people. This live virus vaccine is unusual in that it is to prevent reemergence, not to prevent initial infection. Can the same concept be used for recurrent herpes simplex infection which is much more disabling than herpes zoster in younger people?

Vigyaan CD Part II [NX SERVER]

noreply@blogger.com (Bell) — Tue, 16 May 2006 14:39:00 +0000

Running NX server & accessing it from windows machines.

To start NX server, click on KNOPPIX -> Services ->NX server.

The script is supposed to add a new user called nxuser. However this functionality is not working properly in Vigyaan 1.0. Hence you have to use the root account or the default knoppix account. But by default both these accounts do not have passwords. Hence you have to set a password for both these accounts.

Click on the terminal icon on status bar.
su
passwd
<change the password>
Close the terminal window
System ->kduser
Select knoppix
Uncheck Disable account’
Click Set password and set a new password.

Now on your windows machine download and install nx client from NOMACHINE.

Find the local IP of the vigyaan box by typing ifconfig in a terminal window. Now you can access vigyaan box from your windows machine.

Coiled Coils

noreply@blogger.com (Bell) — Sun, 14 May 2006 06:46:00 +0000

Coiled coils consist of two to five amphipathic alpha-helices that twist around one another to form a supercoil which can be left-handed or right-handed. Left handed ones show a seven-residue periodicity and the right handed one a 11 residue periodicity the stability of which is achieved by a knobs-into-holes packing of apolar side chains into a hydrophobic core.

By modulation of their polar interactions, many different properties like extreme thermo stability can be achieved. Coiled coils are involved in signal transduction or molecular recognition. They provide mechanical stability to cells and are involved in movement process. Charged residues are frequently found at coiled coil interfaces.

The building blocks of IF architecture is an elongated coiled coil region (which inturn contains monomeric 1A and dimeric 1B, 2A and 2B sub segments connected by short linkers) flanked by non helical end domains. The dimeric 2B contains a discontinuity in the heptad repeat pattern called a stutter that creates an undecad repeat which is important for its structural integrity. The highly conserved region within the C-terminus of 2B has an inter-helical and intra-helical salt bridge.

There are several software products to predict the coiled coil region of proteins based on the above structural peculiarities.

References:
Peter Burkhard et al. Coiled Coil: a highly versatile protein folding motif. Trends in Cell Biology 2001:11(2); 82-8

This entry linked to &lt;a&gt;Wikispaces page (coils)&lt;/a&gt;

VigyaanCD

noreply@blogger.com (Bell) — Tue, 02 May 2006 16:43:00 +0000

Setting Up your own Bioinformatics workstation using VigyaanCD

VigyaanCD at
http://www.vigyaancd.org/
has a nice collection of bioinformatics software and is worth downloading. It will boot directly from the CD and needs very little linux expertise as the X-windows system is almost like windows. However I wanted to use it along with windows and I did not want to reboot every time I switch operating system. This is the story of how I set up VigyaanCD on a second hand PIII and use it from my win XP laptop.

I bought a second hand IBM PIII, 450 MHz, 10MB HDD and 128 MB RAM. I formatted the hard disk and added the following partitions
/boot 2GB (ext2), /knophome 6GB (ext2) /knopswap (vfat) /dos (vfat)
My video card supports only 800x600

I copied the CD image to the boot partition with the knoppix tohd =/dev/hda1 command. I created a persistent home directory in /knophome partition and a swap in /knopswap

I start with the following command.
Knoppix screen=800x600 fromhd home=scan noprompt noeject

I will write about how to set up the NX server and run the NX client from laptop to access it in my next post.

This entry linked to Wikispaces page (vigyaanCD)

PLoS Clinical Trials

noreply@blogger.com (Bell) — Fri, 21 Apr 2006 16:18:00 +0000

Clinical trials, particularly randomized trials are critical in delivering reliable evidence about the efficacy of an intervention. Clinical trial data can also provide important information about the potential adverse effects of treatment. Currently, not all trials on human participants are reported in the peer-reviewed literature. PLoS Clinical Trials aims to fill this gap. As an open-access journal, all articles published in the journal will be immediately and freely available online. Join them in supporting these goals, and get your paper read by the widest possible audience: submit your trial results today.
[Download Poster.]

Good Clinical Practice GCP

noreply@blogger.com (Bell) — Sat, 11 Mar 2006 13:53:00 +0000

Good Clinical Practice (GCP) guidelines

GCP has two important goals: protection of the subject, and protection of the data which is possible only through adequate training of all concerned staff. An independent audit is needed to ensure compliance to the standards. US FDA acts as enforcement officers. As they are less flexible unconventional approaches have no scope. European agencies are more flexible but they need to be convinced.

The Declaration of Helsinki issued by world medical association insists that all research subjects must be fully informed about the nature and risks of a clinical trial. Protocol design is a responsibility of the investigator and need to be assessed by the concerned ethical committee. The principal investigator has an overall responsibility over the entire project.

Informed consent which includes signing a consent form and a recruiting interview preferably by the physician is extremely important. Though not absolutely necessary it is a good practice to define and describe in writing how all aspects of clinical research are to be conducted. These standard operating procedures (SOPs) must be followed during the execution of the research.

Translation

noreply@blogger.com (Bell) — Tue, 07 Mar 2006 14:46:00 +0000

Translation

Today I learnt few concepts in protein expression which I found very interesting. As we all know, because of the redundancy of the triplet code, it is possible to preserve aminoacid sequence coding while varying the nucleic acid code. This can even happen as a silent mutation. However the availability of corresponding tRNA for each triplet varies from species to species. The translational efficiency of each code may be different (some times to a very great extend) though all may code for the same product. All silent mutations may not be silent after all.

Few codon pairs exist in relative abundance which may act as translation pause sites and slow down translational process. The tRNAs that bind during the translation of such a biased pair appear somehow incompatible. These codon pairs vary from species to species.

These points need to be considered while designing a gene for expression systems. Designing and implementing an algorithm to optimize the gene with respect to the above points can be a good bioinformatics project.

Gain-of-function mutation

noreply@blogger.com (Bell) — Wed, 01 Mar 2006 18:59:00 +0000

Gain-of-function mutation

Today I learned about a concept (new to me) called gain of function mutation. A mutation in Loricin gene (LOR 730insG) leads to a frame-shift and delayed termination, thus elongating the protein by 22 amino acids. And changing the Gly/Lys-rich domain into an Arg/Leu-rich terminal domain. Instead of being incorporated into the cell envelope, the mutant loricin is translocated into the neucleus as the mutant C-terminus acquires a new function of a nuclear targeting sequence.

The authors have named the resulting phenotype as honeycomb palmoplantar keratoderma with ichthyosis with occasional features like pseudoainhums, prominent knuckle pads and collodion baby. This is however different from Vohwinkel syndrome (hearing impairment but no ichthyosis) and Olmsted syndrome (severe mutilation and periorificial keratotic plaques). The chapter on hereditary PPKs is already a nightmare for dermatology post graduates with umpteen syndromes. The recent advances make it no better.

M.M. Gedicke et al. Palmoplantar keratoderma with mutation in loricin. Brit Journal of Dermatol 2006;154:167-171

Plasmin

noreply@blogger.com (Bell) — Sat, 25 Feb 2006 09:51:00 +0000

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:

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.

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.

DSG3 BJD 2006 Jan 15

noreply@blogger.com (Bell) — Sat, 18 Feb 2006 18:07:00 +0000

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.

Toll-like receptors

noreply@blogger.com (Bell) — Tue, 07 Feb 2006 14:47:00 +0000

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?

UIMA SDK from IBM

noreply@blogger.com (Bell) — Mon, 06 Feb 2006 19:11:00 +0000

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!

Biomedical Research

noreply@blogger.com (Bell) — Fri, 03 Feb 2006 14:06:00 +0000

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.

5UTR

noreply@blogger.com (Bell) — Tue, 31 Jan 2006 20:13:00 +0000

Today I read one article about 5 untranslated region or 5UTR which was a new concept for me. The translational efficiency of mRNA depends on various factors like the context of start codon, AUGs within 5 UTR and the structural stability of mRNA. The authors tried to find out the 5UTR features influencing the translational efficiency by comparing various High expression and Low expression mRNAs. They prepared a database out of this information called LEADER_RNA and the translational prediction algorithm.

help plss in protein structure prediction

noreply@blogger.com (Abhijit) — Mon, 30 Jan 2006 15:44:00 +0000

hi friends,
My name is Abhijit Jadhav.I m doin my graduate project in secondary protein structure prediction using Neural networks.I had few doubts and would be very greatful if you ppl could slove it
1.Is there some benchmark problem for secondary protein structure prediction using neural nets?
2.Is there some neural network solution algorithm for protein structure prediction like RBF networks or SVM?
Thnak you
Abhijit

Molecular Level

noreply@blogger.com (Bell) — Sun, 29 Jan 2006 18:28:00 +0000

Today I came across a very interesting home page belonging to Gale Rhodes, Professor of Chemistry, University of Southern Maine. The tutorials on Swiss PBD and Rasmol are interesting and the bioinformatics tutorial for beginners gives a broad overview which is useful even for the experienced. I have posted the link in the resource manager.

Methotrexate

noreply@blogger.com (Bell) — Tue, 24 Jan 2006 07:55:00 +0000

Psoriasis is essentially a proliferative disorder like Lamellar ichthyosis mentioned below. One of the most effective drugs in psoriasis is methotrexate (MTX). Though traditionally we see MTX as an antifolate drug, this does not fully explain its anti psoriatic effect. Various genetic polymorphisms and its effect on MTX cellular pharmacology are described. Can the Bioinformatics study of MTX polymorphisms and its effect on cell division in relation to mutations in Lamellar Ichthyosis (Which are very well characterized unlike Psoriasis) be useful? Post your thoughts here and contact me http://www.gulfdoctor.net/research.htm if you interested in exploring this together.

Lamellar Ichthyosis

noreply@blogger.com (Bell) — Sun, 22 Jan 2006 19:10:00 +0000

Lamellar Ichthyosis
Today a gentleman from UK came to me with photographs of his cousin with a rare autosomal recessive condition called ‘Lamellar Ichthyosis’ which I have posted in my Dermatology Blog. A review of literature shows that patients with lamellar ichthyosis have accelerated epidermal turnover with proliferative hyperkeratosis, in contrast to retention hyperkeratosis which is more common. This involves a mutation in the gene for transglutaminase 1 (TGM1). The transglutaminase 1 enzyme is involved in the formation of the cornified cell envelope. Please comment on the scope of exploring the TGM1 mutations with respect to this rare form of proliferative hyperkeratosis.

Welcome

noreply@blogger.com (Bell) — Sat, 21 Jan 2006 11:19:00 +0000

Welcome to BioBlog @ GulfDoctor.net

I have designed three web applications for the bioinformatics community.

First is an application to manage online resources for bioinformatics. You can add your links and invite others to see your links. You can maintain a list of your favourite links. There is a comprehensive search facility too. The database already contains more than 500 links.
Second is an application to discuss a particular topic in bioinformatics. You can invite others to view your discussion and opine. You can also post related sequences and do blast search directly from the site.
Both applications are combined under a single login here.
Third is a bulletin board for bioinformatics where you can post a sequence along with a message and annotate a particular region.

Visit my Group Research Page!