Introducing BioDec ...

BioDec S.r.l.Via Calzavecchio 20/2

I-40033 Casalecchio di Reno (BO)info@biodec.comwww.biodec.com

● Bioinformatic turnkey solutions

● Bioinformatics consulting

● Biosequence DB annotation pipelines

● Web applications

● System integration

Close ties to UniBo Biocomputing Unit(www.biocomp.unibo.it)

2/25

Bioinformatic turnkey solutions• Integrated solutions:

• Bioinformation / Lab Data Management System - CMS-based lab data, diary and workflow management;

• Molecular Anthropology - Haplogroup tree browsers;• Plone4bio - CMS-based biosequence management and

annotation software.• Decoders (predictors).

Bioinformatics Consulting• Development, engineering and integration of custom software;• Annotated databases of biosequences (e.g. genomes).

Our Forte• Bioinformation management;• Machine-learning methods and annotation pipelines;• Web applications.

Business Activities

3/25

Bioinformation Management System

A bundle including Plone4Bio, the annotated databases, and BioDec's own lab data management software, to collect, manage and analyse laboratory data from specific molecular biology techniques.

• Lab diary, recording aims and conditions of the experiment, including structured pages for the recording of experimental data, specific of each technique. Data may include digital images, and may be shared within a working group or an organization according to flexible, entirely user-defined security levels. Presently supports:

● Immunogenic assays (due 1 st quarter 2010);

● Polymerase Chain Reaction techniques;

● Electrophoresis blot techniques.

• Customizable workflows are supported, and may differ for specific techniques or Customer specifications, thus ensuring a full match between the rules applied in the lab and the data lifecycle.

4/25

BioDec BMS screenshots

BioDec BMS - PCR test blot view

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BioDec BMS screenshots

BioDec BMS - PCR test summary view

6/25

BioDec BMS screenshots

BioDec BMS - PCR protocol definition

7/25

● An application for the management of molecular antropology data

● Allows to store, inspect, search and retrieve data through the familiar interface of a standard web browser

Haplone

8/25

● Population subsets can be easily selected (by location, haplogroup, sex, MRCA) using simple query forms, whose reports also provide basic statistics and charts on the selected sets.

● By leveraging on Plone access-control features, the application can handle selective access to stored data, allowing fine-grained control on what it can be accessed by an anonymous vs an authenticated user, so it can be used both for internal information sharing and data dissemination simultaneously.

Haplone screenshots

9/25

● Data are stored in the "Subject" data structure,

containing both personal and molecular data.

● For each subject, the application calculates on-the-fly the haplogroup, based on its tested UEPs, as well as the most recent common ancestor for each sexual lineage, based

on the stored population. ● The system also takes care of

checking data consistency and flags the user for potential

errors, such as inconsistent or conflicting UEPs or out-of-range STRs within a given

Haplone screenshots

10/25

● A Plone-based (http://plone.net), feature-rich graphic BioSQL browser, to search and explore data and metadata (annotations) from biosequence databases. May integrate custom-made predictors (“Decoders”);

● We publicly released the base version, including an example predictor and documentation, as open-source software, available from http://plone4bio.org;

● Plone4Bio is reliable and modular, and is the basis of BioDec commercial software bundles.

Plone4Bio

11/25

Plone4Bio screenshots

Plone4bio “Add new...” menu

12/25

Plone4bio LiveSearch result

Plone4Bio screenshots

13/25

Plone4bio “Show sequence features”

Plone4Bio screenshots

14/25

User-managed pipeline for biosequence analysis and comparison, providing:

● Full CMS features: several standard and user-defined content types (including files, pages, RSS feeds...);

● Full set of Decoders: to annotate biosequences from any database;

● User-defined biosequences: customer's own biosequences may be instantiated and populated;

● Annotated databases: our decoders have been used to annotate and cross-link public databases sections from Uniprot, NCBI and Ensembl, thus providing a reliable and meaningful metadata set. Custom annotated databases are available on request.

Plone4Bio commercial release

15/25

Tools from machine learning

TTCCPSIVARSNFNVCRLPGTPEAICATYTGCIIIPGATCPGDYAN

Prediction

Known sequences (DB subsets)

ANN,HMM,SVM

Known mapping

GeneralRules

Knownstructures

New sequence

• Artificial Neural Networks (ANNs) • Hidden Markov Models (HMMs)• Support Vector Machines (SVMs)

ANN,HMM,SVM

16/25

Papers about our decoders have been published in journals such as Bioinformatics, Journal of Molecular Biology, Nucleic Acids Research.

BioDec Decoders

Protein sequence tools

● Transmembrane all-alpha sequence

● Transmembrane all-beta sequence

● Signal peptide

● GPI-anchoring prediction

● Coiled-coil segment prediction

● Disordered region prediction

● Subcellular localization prediction

● Sequence classification

Protein Structure tools

● Interaction patch prediction

● Fold recognition and modelling

RNA tools

● siRNA design

Our toolbox is built to be MODULAR,so we can assemble analysis systems

according to your specifications.

17/25

● Interaction patch decoder

● Analyzes protein solvent-exposed surface for putative “interactor” residues, returning a “fuzzy” (probabilistic) answer.

● Interactors are correlated and grouped into patches.

● Results are mapped on the protein 3D structure and made available through a web interface.

Contact-shell profile

Int non-Int

A BioDec Decoder: ZenDock

18/25

• Angler, a Pipeline for the annotation of proteome biosequences such as prokaryotic proteomes, is used to select candidates for epitope selection.

• The annotation results (“Proteome Atlases”) are published in annotated databases.

Angler classifies gram-negative proteome sequences into nine

different classes, including the all-beta membrane proteins and the soluble secreted proteins, most

relevant to vaccine development.

Case study - Searching for the “membrane fraction” of a bacterial proteome

Proteome

Generateprofiles

Predictions:✔ Signal peptides✔ Betabarrels✔ Alpha-helical TMP✔ Fold recognition✔ Coiled coils✔ Disordered regions

Classify:9 classes

ProteomeAtlas

19/25

EcoGene Knowledge Base (E. Coli K12)

Accuracy CoverageAll-alpha TMP 92.3% 92.6%All-beta TMP 86.7% 75.0%Soluble 96.9% 95.9%

All-alpha TMPs represent less than 20% of a proteome.All-beta TMPs represent less than 5% of a proteome.

Angler performance

Porin (Rhodobacter capsulatus)

Bacteriorhodopsin(Halobacterium salinarum)

Bilayer

β-barrel α-helicesOuter Membrane Inner Membrane

20/25

• Sirena, a siRNA design engine, used two very large, consistent and independent data sets from the literature: one for fitting, the other for testing.

• Based on machine-learning: Neural Network.

• Prediction is performed on a 19nt input window.

• Input is the sequence and the sequence composition for each window in the mRNA sequence.

• Output is an estimated knock-down efficiency (Q).

• Around 70% of the reported candidates are expected to have experimental knock-down efficiency greater than 80%.

• Successfully field-tested by TargetHerpes virologists.

TargetHerpes.org

Case Study - siRNA Design

21/25

I have a compound library active on some receptors subclasses.

Q.: Which sequences in the Human genome may be targeted by my library?

Case study - Discovering new receptors of pharmaceutical interest

22/25

Train

● Find all known, classified receptors.

● Build a MSA using both sequence and 7TM-topology informations.

● From MSA, derive and partition a classification tree.

● Train class-specific HMMs.

Predict

● Scan Human genome using our “Septimus” tool to find putative new 7TM-receptors.

● Classify using the class HMMs.

BioDec's approach

23/25

● Consistent 7TM prediction for all the targets, useful for receptor modelling.

● Some newly-classified targets have been succesfully validated.

– New targets– New lead molecules

Success

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● ZenDock: multiple analysis on each available structure then consensus.

● Predicted a new potential interaction site.

● Very good agreement between prediction and experiments.

● Peptide found is now a new-drug lead.

Case study - blocking protein-protein interaction

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BioDec S.r.l.Via Calzavecchio 20/2

I-40033 Casalecchio di Reno (BO)info@biodec.comwww.biodec.com

Thank you