Tuesday, May 20, 2008

Faster way to screen nonribosomal peptides

Bandeira et al. in the paper "De Novo Sequencing of Nonribosomal Peptides" ( http://www.springerlink.com/content/n532545722750915/ ) outline a strategy based on MS alignment leading to faster nonribosomal peptides (example penicillin) screening. This has potential to hasten the process of finding new drugs (better say candidates?).
clipped from www.genengnews.com

If you imagine the structure of an NRP as a cyclic string of beads, then the new algorithms both decipher the mass of each bead based on the mass spectrometry and determine the order of the beads within the ring crucial pieces of information for uncovering both the structure of the molecule and its pharmacological activities.

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Monday, May 12, 2008

Rosendal Meet



I was attending the Rosendal meet (from 6-8 th May, 2008) between members of CBU (Computational Biology Unit ... and Department of Informatics, University of Bergen, Norway) and MB-NIMR (Division of Mathematical Biology at National Institute for Medical Research, MRC, London group, UK).
Thanks to Xianjun for posting the pictures from the trip at http://picasaweb.google.com/sterding/Rosendal2008 (the beautiful pic above is coming from there) and Anders at http://flickr.com/photos/lanzen/sets/72157605097913531/ . The ones from my camera are available at http://picasaweb.google.com/sharma.animesh/Rosendal_meet?authkey=wFgJVxkGwTU .

Monday, May 5, 2008

Workshop: BREW 2008

I was in Bielefeld, Germany for BREW2008 workshop. I was quite suspicious of this place as people (http://www.cebitec.uni-bielefeld.de/index.php?option=com_cudbhome&task=show&cudbname=sniemeie , http://www.cebitec.uni-bielefeld.de/index.php?option=com_cudbhome&task=show&cudbname=twittkop ) informed me that Bielefeld does not exist ( http://en.wikipedia.org/wiki/Bielefeld_Conspiracy )! So I went out and took loads of snaps ( http://picasaweb.google.com/sharma.animesh/BREW2008?authkey=ranwczoE2-Q ) to prove its existence ... well on second thought map is not the territory ( http://en.wikipedia.org/wiki/Thomas_Kuhn ).
Coming back to the workshop, this is a nice event with a great concept ( http://bib.oxfordjournals.org/cgi/content/abstract/9/3/250 ) organised by and for people from:
* International Graduate School in Bioinformatics and Genome Research, University of Bielefeld, Germany ( http://www.cebitec.uni-bielefeld.de/gradschool/ )
* Molecular and Computational Biology Research School, University of Bergen, Norway ( http://www.mcb.uib.no/ )
* Max Planck Research School for Computational Biology and Scientific Computing (IMPRS-CBSC), Berlin, Germany ( http://www.imprs-cbsc.mpg.de/ )
* EBI PhD Program, European Bioinformatics Institute, England ( http://www.ebi.ac.uk/ )
* ComBi Program, University of Helsinki, Finland ( http://www.cs.helsinki.fi/ )
I had a great time there and would recommend people from the above list to go for BREW 2009 which is tentatively scheduled after a year at http://www.cs.helsinki.fi/ ... (?)

BREW 2008

Bioinformatics Research and Education Workshop, Bielefeld, Germany April 28-30 2008


  • March 1th -- Abstract submission deadline

  • March 7th -- Paper submission deadline

  • March 20th -- Review deadline

  • April 11th -- Deadline for final version of paper

  • April 28th -- Meeting in Bielefeld

About BREW

BREW aims to give an introduction to scientific conferences, including submission, peer review
and presentation of scientific papers. All participants must submit a paper
and take part in reviewing papers from other participants in order to attend the workshop.
After the review deadline, you have a chance to make alterations to your paper
and deliver a final version. All participants will present their paper at the meeting in April.


BREW is held in an around-robin fashion each year at the participating PhD programs:
Bergen (2007),
Cambridge (2006),
Berlin (2005),
Helsinki (2004),
Bielefeld (2003), and
Hinxton (2002).

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Tuesday, April 22, 2008

The model beetle and pest genome sequenced

clipped from www.nature.com
Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell–cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development.
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Monday, April 21, 2008

Free UCSC Genome Browser Training

OpenHelix is providing free UCSC Genome Browser training for Institutions. You can apply for this at http://www.openhelix.com/seminars .

"The three and half hour introductory tutorial will cover the topics needed to effectively use this powerful, free, publicly-accessible tool, including: basic functionality of Genome Browser searching and BLAT use, Table Browser use, creating and using Custom Tracks, and an introduction to the Gene Sorter.
Participants will receive slide hand-outs, exercises, and a UCSC Genome Browser and Table Browser Quick Reference Cards."
clipped from www.openhelix.com

To bring the seminar to your institution, apply at www.openhelix.com/seminars.  The only two requirements from the institutions are:
-Providing a computer classroom with internet access.  Preferred number of computers is 24 or above. An alternative to a computer room is having wireless available and participants bringing their own laptops. The seminar can be done in the morning and repeated in the afternoon, to reach more users.


 - Conduct outreach and communication to participants as necessary.

 
The number of seminars is limited, so apply today.

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Friday, April 18, 2008

Some Unnatural Base Pair for DNA strings ...

From the base of F1000, I got hold of this exciting discovery (invention may be?) "Discovery, Characterization, and Optimization of an Unnatural Base Pair for Expansion of the Genetic Alphabet" [ http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/2008/130/i07/abs/ja078223d.html ] from Leconte et al. at Scripps [ http://www.scripps.edu/ ]. Seems like the bioinformaticians will be getting more and more new symbols to there vocabulary!
clipped from pubs.acs.org

DNA is inherently limited by its four natural nucleotides. Efforts to expand the genetic alphabet,
by addition of an unnatural base pair, promise to expand the biotechnological applications available for
DNA as well as to be an essential first step toward expansion of the genetic code. We have conducted two
independent screens of hydrophobic unnatural nucleotides to identify novel candidate base pairs that are
well recognized by a natural DNA polymerase. From a pool of 3600 candidate base pairs, both screens
identified the same base pair, dSICS:dMMO2, which we report here. Using a series of related analogues,
we performed a detailed structure-activity relationship analysis, which allowed us to identify the essential
functional groups on each nucleobase. From the results of these studies, we designed an optimized base
pair, d5SICS:dMMO2, which is efficiently and selectively synthesized by Kf within the context of natural
DNA.

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Thursday, April 17, 2008

Darwin's first draft ...

This site contains Darwin's complete publications, thousands of handwritten manuscripts and the largest Darwin bibliography and manuscript catalogue ever published;

also hundreds of supplementary works: biographies, obituaries, reviews, reference works and more.

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Conference: Genomes 2008 (11 th April) - Closing Session


The last session started with Hilde De Reuse talking about "Nickel trafficking in the gastric pathogen Helicobacter pylori". She talked about gastric colonization of H.pylori and its secret survival weapon, the Urease. She also mentioned that she will never like her child to be infected with this nasty bug called H.pylori ( c.f. Martin J. Blaser opening talk).
Uri Gophna [ about "Complexity, connectivity, and the fate of laterally acquired genes". His analysis on horizontal gene transfer using E.coli as model challenged the Complexity theory (genes coding for protein which form part of protein complex in donor genome do not tend to successfully integrate in recipient genome) and came up with Balance theory (protein coded by transferred genes integrate gradually into pre-existing protein complexes in recipient). Mark Pallen [ about "Escherchia coli: Pathogenomics of a model organism" and argued that O-island 115 is a deletion in K12 and not a insertion in O157:H7 E.coli strain. Ben Adler [ about "What can we learn from comparative genomics of Leptospira species?". He started his talk by pointing to the fact that what Leptospira might be thinking about sequencing..."you have got my gene, but you don't really know me"!
This fine conference ended with the closing talk from Frank Kunst :)

Its time to walk in the streets of Paris now ...
Session 8: Comparative Genomics and Evolution
Chair: Xavier Nassif, Necker Hospital, Paris, France

Hilde De Reuse, Institut Pasteur, Paris, France
Nickel trafficking in the gastric pathogen Helicobacter pylori

Uri Gophna, University of Tel Aviv, Tel Aviv, Israel
Complexity, connectivity, and the fate of laterally acquired genes
Mark Pallen, The University of Birmingham, Birmingham, United Kingdom
Escherchia coli: Pathogenomics of a model organism
Ben Adler, Monash University, Victoria, Australia
What can we learn from comparative genomics of
Leptospira species?
Closing lecture
Frank Kunst, Institut Pasteur, France

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Conference: Genomes 2008 (11 th April) - S8

Session opened with Erick Denamur talking about insertion and deletion hotspots of E.coli. He also talked about the coliscope consortium which is "a sequencing project for the understanding of commensalism and virulence emergence in the Escherichia coli/Shigella species". Then the mic was handed to Carmen Buchrieser who highlighted the importance of Legionella which made the Queen run back to the palace. The following talk was from Tim Stinear who mentioned how poking finger(s) into fish can lead to Mycobacterium marinum (which along with M.ulcerans, is closest to M.tuberculosis giving positive mantoux test) infection! He also mentioned about Gene Spaghetti a cool tool for "visualizing base and amino acid usage in a genome", COG's 3-way genome blast approach and synteny map generation. Model of successive binary fission in E. coliImage via WikipediaThen came Marrion karrasch who talked about ERA-NET PathoGenoMics, Interferon interference (?), invasive propeties of C.albican (with liver capsule invasion as an example) and RNAi for possible therapeutic approach (?). Again thanks to Swati for the better notes below:

Population phylogenomics of the E.coli species
Erick Denamur, medical faculty Xavier Bichat, Paris

- Phylogeny of complete genome within species.

- Majority of E.coli strain can be assigned to one of 4 main phylogenetic groups (A, B1, B2 and D).

- These 4 phylogenetic groups differ in their phenotypic and genotypic characteristics.

- Gene conversion doesn’t affect the tree topology.

- E.coli ancestor is close to K-12






    Comparative Genomics of Legionella pneumophila and Legionells longbeachae, ttwo human pathogens that coevolved with protozoa.
    Carmen Buchrieser, Pasteur Institute, Paris


- Analysed and compared the whole genome to understand the pathogencity.



Session 8: Comparative Genomics and Evolution
Chair: Agnès LABIGNE, Institut Pasteur, Paris, France
Erick Denamur, Medical Faculty Xavier Bichat, Paris, France
Population phylogenomics of the Escherichia coli species
Carmen Buchrieser, Institut Pasteur, Paris, France
Comparative genomics of Legionella pneumophila and Legionella longbeachae, two human pathogens that coevolved with protozoa
Tim Stinear, Monash University, Victoria, Australia
Insight into tuberculosis and Buruli ulcer from the complete genome sequence of Mycobacterium marinum
Pathogenomics PhD award
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Conference: Genomes 2008 (11 th April) - S7

Overview of three-hybrid assay.Image via Wikipedia
I joined the session when Fiona Brinkman was saying that hyperthermophilic bacterias have higher number of cytoplasmic protein. Later came Alexei Savchenko who was speaking that pathogens manipulate the host signalling for their benefit (e.g. uibiquitination). He also mentioned that Toronto centre has target of getting 60 high quality pdb structure per year and also look at these for catalytic activity using enzymatic assay. For more on this session, I took the nice notes from Swati which are pasted below:

The tubercle bacilli: Molecular determinants of pathogenicity and attenuation.

  • Comparison between virulent strains and strains that have lost their ability to cause disease.
  • RD1 was absent in M. Bovis BCG and microti but present in virulent strains.
  • RD1 codes for ESAT-6 and ESX-1.
  • Biologically relevant model of ESAT-6 and its protein partner CFP-10 was generated. ESAT-6 and CFP-10 was involved in the host-pathogen interation.
  • Finally it was found that PhoP/PhoR was involved in the regulation of ESAT-6 secretion.


Generating protein interaction map for pathogens using yeast two hybrid.
Russel L. Finley, Wayne State University, Detroit, USA


    - Organism- Campylobacter jejuni

        • Two-hybrid system used to generate a protein interaction map.
        • The map includes thousand of interaction and covers 80% of C. jejuni proteins.
        • This approach is used to find the protein functions, pathway structure and potential new drug target for C. jejuni.






Insights into the evolution of pathogens using improved bioinformatics approaches.
Fiona Brinkman, Simon Fraser University, Canada


    - Computational methods for the predication of protein subcellular localization, predication of genomic island and identification of orthologous.

      • Used VFDB (most robust curated database)

    - Signature tagged mutagenesis data

    - Analysed 100 pathogens and nonpathogens.

    - Increase in Genome size = Increase in networks

      • Genomic Island plays an important role in evolution.

    - Certain offensive virulence factor associated with







Genomewide structural and biochemical annotation of uncharacterized proteins from pathogenic bacteria.
Alexei Savchenko, University of Toronto, Canada

    - Selected uncharacterized proteins from pathogenic bacteria.

      • How the protein purification was done?
      • Used X-ray to determine protein structure.
      • Designed enzymatic assays to screen purified proteins for enzymatic activity.
      • Biochemical characterization of protein was determined by the application of secondary screens with natural substrate.

- The main focus of this study was to annotate effectors proteins from Shigella flexneri cause shigellosis in humans.





Session 7: Computational, Structural Genomics and Systems Biology
Chair: BennoSCHWIKOWSKI, Institut Pasteur, Paris, France
Russel L Finley Jr, Wayne State University, Detroit, USA
Generating protein interaction maps for pathogens using yeast two-hybrid
Jörg Stelling, ETH Zürich, Switzerland
Systems analysis of signal transduction pathways
Fiona Brinkman, Simon Fraser University, Burnaby, Canada
Insights into the evolution of pathogens using improved bioinformatics approaches
Alexei Savchenko, University of Toronto, Toronto, Canada
Genomewide structural and biochemical annotation of uncharacterised proteins from pathogenic bacteria
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Conference: Genomes 2008 (10 th April) - S6

Session opened with talk from Jean Weissenbach
who talked about mining metagenomes with focus on di-codon frequency and GC content, followed by a talk from Victor de Lorenzo and George Weinstock
who mentioned that error rates are pretty low for 454 data compared to Solexa and looking at the price decrease from 2 runs for 20K/genome to 2K/genome with 500b reads, 454 is going in a good direction :)
For more, check out the previous post ( http://computationalbiologynews.blogspot.com/2008/04/conference-genomes-2008-10-th-april-s5.html ) for notes from Anders.

clipped from www.pasteur.fr
Session 6: Microbial Metagenomics
Chair: Didier MAZEL, Institut Pasteur, Paris, France
Jean Weissenbach, Genoscope, Paris, France
Mining metagenomes
Victor de Lorenzo, Centro Nacional de Biotecnología, Madrid, Spain
Debugging and reconstructing regulatory networks of
Pseudomonas putida for environmental release
George Weinstock, Baylor College, Huston, USA
Approaching the Human Microbiome
Session 6: Microbial Metagenomics
Chair: Hilde DE REUSE, Institut Pasteur, Paris, France
Karl O. Stetter, University of Regensburg, Germany
The Hyperthermophilic Archaea
Virginia Armbrust, University of Washington, USA
Life in the sea: new insights from diatom genomes
Lena Tasse, INSA Toulouse, Toulouse, France
Screening of the human intestinal microbiota for the discovery of new enzymes specific for fiber degradation

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Conference: Genomes 2008 (10 th April) - S5

I was present in Tracy Palmer's talk who works on The Tat protein export pathway
and Mariagrazia Pizza who works in the area of vaccine discovery , more specifically Serogroup B Meningococcus . Later Athanasios Typas came and talked about GIANT coli system for determining genetic interactions (12X12 plate with pixel marked borders followed by inplate normalization and central substraction, the image thus obtained can be compared across similar experiments).

P 700Image via Wikipedia



Thanks to Anders for taking the below notes:

Environmental (meta)genomics

  • Metagenomics of digestive tract (Dusko Ehrlich, INRA)
    • 10x more cells than human body, ~1000+ species
    • MetaHIT project, attempt to find genes that
      • Are required for life in the gut
      • Has relation to obesity or intestinal bowel disease
    • Identification of COGs in current data (700M) and comparison to wetlab results. Few interesting results. (I would avoid COGs)

  • Viral photosynthesis (*Odded Beja, Technion, Israel)
    • Bacteriophages encode parts of photosystem II
      • To maintain photosyntehsis during infection
      • More destructive to host
    • Viral encoded such genes cluster phylogenetically

    (either using alignment or PCA analysis of nucleotide freq.)


  • Nanostructur-Initiator MS (Trent Northern)
  • Predicting Biological Function at different levels (Peer Bork)
    • Reconstruction of metabolic community network from homology searches + prot. Interaction data (STRING)
    • “Full of pitfalls and dependencies”
    • Impressive soil sample from Mexican salt swamps
      • 454 data from 10 layers!
      • Mapped to consensus metabolic network (somehow)
      • Comparison between layers




clipped from www.pasteur.fr
Session 5: Functional Genomics
Chair: Brendan WREN, London, United Kingdow
Susan Gottesman, Nat. Cancer Inst., Bethesda, USA
Small RNAs and
E. coli regulatory circuits
Peer Bork, EMBL, Heidelberg, Germany
Predicting biological function at different scales
Tracy Palmer, University of Dundee, Dundee, United Kingdom
Functional genomic analysis of protein secretion in
Streptomyces species
Mariagrazia Pizza, Novartis Vaccines, Italy
Microbial genomes as basis of vaccine discovery: the Meningococcus B challenge
Athanasios Typas, University of California at San Francisco, San Francisco, USA
The first high-throughput system for quantitatively assessing genetic interactions in bacteria

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