BIOLOGY BEYOND BORDERS
PARADIGM OF TB INFECTION: CAUSE INFECTION IN MANY BUT ACTIVE DISEASE IN FEW.
DYNAMIC INTERPLAY OF HOST AND PATHOGEN INTERACTIONS
SATGES OF TUBERCULOSIS INFECTION:
BUG TAKENS UP BY ALVEOLAR MACROPHAGES > PREVENTION OF PAHAGO-LYSOSOMES FROMATION AND RAPID BACTERIAL MULTIPLICATION > RELEASE OF CHEMOTACTIC SIGNALS
PROGRESSION OF GRANULOMA TO ACTIVE TUBERCULOSIS
Saturday, April 10, 2010
Low-Cost Automation of Sputum Smear Analysis by Imaging Cytometry------Pavak shah
Smear Microscopy Advantages: Low Cost
Low-Cost imaging: low-magnification; LED excitation; CMOS camera sensor; fixed focus, fixed-stage; Smear analysis automation
Advantages: Low-cost; potential high sensitivity
Image Analysis: many possibilities, simplest approach: segment image by intensity threshold; more sophisticated strategy: shape space classifier
Why imaging cytometry?
low-cost, low-power; portable, easily ruggedized, temperature stable reagents, increses testing throughput.
Continued and future development: software- image analysis optimization
Low-Cost imaging: low-magnification; LED excitation; CMOS camera sensor; fixed focus, fixed-stage; Smear analysis automation
Advantages: Low-cost; potential high sensitivity
Image Analysis: many possibilities, simplest approach: segment image by intensity threshold; more sophisticated strategy: shape space classifier
Why imaging cytometry?
low-cost, low-power; portable, easily ruggedized, temperature stable reagents, increses testing throughput.
Continued and future development: software- image analysis optimization
TB POC test------martin casenghi
TB diagnosis, closest POC test: Sputum smear microsope
TAG: Treatment Action Group
Medical needs priorities
The TB POC test Challenge: Ag and /or Ab detection, funding gap.
Alternative funding mechanism -TB diagnostic prize fund?
TAG: Treatment Action Group
Medical needs priorities
The TB POC test Challenge: Ag and /or Ab detection, funding gap.
Alternative funding mechanism -TB diagnostic prize fund?
Glycomics---- Sulagana Banerjee
Glycosylation
carbohydrate interactions in a cell.
Why glycans?
Glycans: potential drug targets for drugs, vaccine candidates, enzymes processing glycans catalyze steps in growth, proliferation and infection diseases.
Through th Looking Glass--
Glycome in infection development: microbial adhesion > host penetration > host damage
Glycosysltion present in both prokaryotes and eukaryotes
Two types of glycans: N-Glycans and O-Glycans
Key components for targeting glycome: enzymes responsible for makin glycoconjugate; protein responsible for making cell surface.
Challenges for annotatinng the Mtb glycome: not much available literature.
Organisation of Glycome in Mtb:
Re-annotating Mtb using the power of collaboration
Search for homologues of glycans
Function prediction of unknown proteins
carbohydrate interactions in a cell.
Why glycans?
Glycans: potential drug targets for drugs, vaccine candidates, enzymes processing glycans catalyze steps in growth, proliferation and infection diseases.
Through th Looking Glass--
Glycome in infection development: microbial adhesion > host penetration > host damage
Glycosysltion present in both prokaryotes and eukaryotes
Two types of glycans: N-Glycans and O-Glycans
Key components for targeting glycome: enzymes responsible for makin glycoconjugate; protein responsible for making cell surface.
Challenges for annotatinng the Mtb glycome: not much available literature.
Organisation of Glycome in Mtb:
Re-annotating Mtb using the power of collaboration
Search for homologues of glycans
Function prediction of unknown proteins
Pathway Modelling and Curationusing CellDesigner + Payao --Yukiko
CellDesigner
How to Build Pathway?
species (nodes)
reaction
litreature
Model Representation <> Modelling tools <> Databases
SBML (Systems Biology Markup Language)
SBGN (Systems Biology Graphical Notation):
MAPK pathway
SBML <> SBGN
Read SBML file, add graphical notation, stored in CD annotation
Database Connection
Annotation:
Notes: model, species, protein/RNA/DNA;
MIRIAM;
Layer text
Simulation: via control panel; via SBW menu
SBW= systems biology workbench
SBML features and supporting tools
Models For Simulation
Plugin Development
Model Curation
Pathway Modelling Case Study
Mapathon: 15 members: ERATO wet lab virologists/biologists etc.
read 60 papers
Payao: community base pathway enrichment paltform
Public> Map> Community A
How to Build Pathway?
species (nodes)
reaction
litreature
Model Representation <> Modelling tools <> Databases
SBML (Systems Biology Markup Language)
SBGN (Systems Biology Graphical Notation):
MAPK pathway
SBML <> SBGN
Read SBML file, add graphical notation, stored in CD annotation
Database Connection
Annotation:
Notes: model, species, protein/RNA/DNA;
MIRIAM;
Layer text
Simulation: via control panel; via SBW menu
SBW= systems biology workbench
SBML features and supporting tools
Models For Simulation
Plugin Development
Model Curation
Pathway Modelling Case Study
Mapathon: 15 members: ERATO wet lab virologists/biologists etc.
read 60 papers
Payao: community base pathway enrichment paltform
Public> Map> Community A
Friday, April 9, 2010
COMPUTATIONAL SYSTEMS BIOLOGY- Tools & aPPLICATION-Samik Ghosh (The System Biology Institute)
PART I
PATHWAY CURATION TOOLS AND APPLICATION
Complexity: Guess which body was not designed to stand turbulence?
Post genomic era has opened up huge database cataloguing the molecular parts of biological systems; Comprehansive knowledge of isolated systems available 'in vitro' and in vivo; Comprehanding paradigm shift
Computational Approach:
Model-Modify-Mine-Measure
Biological Modelling and simulation:
Body waeight> Tissue/cells > Protein > Genes (Top-Down: increasing complexity but Bottom-Up: increasing abstraction)
System biology Approach: network model construction (clinical data, animal models, biologicalliterature); network property analysis (pathway length distribution, node centrality distribution, network degree distribution); high granularity pathway dynamic modelling (celldesigner.org)
Computational Platform:
GN (graphical notation), SBML, CellDesigner.org, CellDesigner Applet, Public Donation Database
PART II
Mtb Mappathon
PATHWAY CURATION TOOLS AND APPLICATION
Complexity: Guess which body was not designed to stand turbulence?
Post genomic era has opened up huge database cataloguing the molecular parts of biological systems; Comprehansive knowledge of isolated systems available 'in vitro' and in vivo; Comprehanding paradigm shift
Computational Approach:
Model-Modify-Mine-Measure
Biological Modelling and simulation:
Body waeight> Tissue/cells > Protein > Genes (Top-Down: increasing complexity but Bottom-Up: increasing abstraction)
System biology Approach: network model construction (clinical data, animal models, biologicalliterature); network property analysis (pathway length distribution, node centrality distribution, network degree distribution); high granularity pathway dynamic modelling (celldesigner.org)
Computational Platform:
GN (graphical notation), SBML, CellDesigner.org, CellDesigner Applet, Public Donation Database
PART II
Mtb Mappathon
System Biology
whole > sum of its part
What system biology not... NOT a black office, NOT a Spherical Cow',
A matter of sacle- physics, chemistry , biology
A Fundamental Difference-- physics, chemistry= predictive, but, biology= observational
Making biology a predictive science
why do we need computational modelling?
A new way of drug design- system focus<- target focus<- legend focus Reconstruction of Metabolic Networks Practice of systems biology Stoichiometric Analysis- capture the structure of metabolic network, does not require quntitative kinetic parameters, FBA (Flux balance analysis) Work Flow of FBA -- Development of pathway model-> computation of stoichiometric matrix-> FBA-->in silico gene deletions-> drug perturbations-> identification of protein essential to pathway-> Drug target
Mycolic Acid Biosynthesis Pathway
Reactome Modelling -- Pathway Modelling (FBA), Network Modelling
Reaction Networks: Comparative Analysis
targetTB: Target Identification Pipeline
Network Analysis- Node deletions: change in netwok parameters; Lethal Deletions
Interactome Construction
Structure Analysis
PocketDepth: Binding pocket detection
PocketMatch- A new algorithm for Binding site comparison
Protein-Protein Influence Matrix: identify maximally connected code; Preliminary analysis shows hub involvement.
High Order Interactions: Pathway-Pathway; Process-Process
Pathways to Drug Resistant
Model Summary: model construction from litreature, Boolean construction, 75 nodes are present.
State MAP for simulations
MAP of single & double knock-outs
work flow- host pathogen modelling: advantage of modelling- bird's eye view for host-pathogen interplay
Genomics-> Proteomics-> System Biology
whole > sum of its part
What system biology not... NOT a black office, NOT a Spherical Cow',
A matter of sacle- physics, chemistry , biology
A Fundamental Difference-- physics, chemistry= predictive, but, biology= observational
Making biology a predictive science
why do we need computational modelling?
A new way of drug design- system focus<- target focus<- legend focus Reconstruction of Metabolic Networks Practice of systems biology Stoichiometric Analysis- capture the structure of metabolic network, does not require quntitative kinetic parameters, FBA (Flux balance analysis) Work Flow of FBA -- Development of pathway model-> computation of stoichiometric matrix-> FBA-->in silico gene deletions-> drug perturbations-> identification of protein essential to pathway-> Drug target
Mycolic Acid Biosynthesis Pathway
Reactome Modelling -- Pathway Modelling (FBA), Network Modelling
Reaction Networks: Comparative Analysis
targetTB: Target Identification Pipeline
Network Analysis- Node deletions: change in netwok parameters; Lethal Deletions
Interactome Construction
Structure Analysis
PocketDepth: Binding pocket detection
PocketMatch- A new algorithm for Binding site comparison
Protein-Protein Influence Matrix: identify maximally connected code; Preliminary analysis shows hub involvement.
High Order Interactions: Pathway-Pathway; Process-Process
Pathways to Drug Resistant
Model Summary: model construction from litreature, Boolean construction, 75 nodes are present.
State MAP for simulations
MAP of single & double knock-outs
work flow- host pathogen modelling: advantage of modelling- bird's eye view for host-pathogen interplay
Genomics-> Proteomics-> System Biology
MANAGING AND ANNOTATING M.Tb DATA USING DrugPedia AND MycoTB---G.P.S. Raghava
`INTRODUCTION
IN SILICO APPROACH
- SEARCHING POTENTIAL DRUG TARGETS, DESIGNING EFFECTIVE INHIBITORS, MANAGING AND ANNOTATING M. TUBERCULOSIS DATA
INVOLVEMENT OF PUBLIC AGAINST WAR
- OSDD IS A PLATFORM, C2DIS A EXPERIMENT TO INVOLVE STUDENTS, EFFECT USE OF PUBLIC IS CHALLENGE.
MANAGING AND SHARING OF DATA
-TRADITIONAL DBMS ARE RIGID, ANNOTATING PROBLEM IS NOT DEFINED PRBLEM, NEED OF FLEXIBLE DBMS (MycoTB)
DrugPedia PLATFORM FOR SHARING DATA.
CRDD: COMPUTATIONAL RESOURCE FOR DRUG DISCOVERY
C2D: ANNOTATING OF M.Tb PROTEOME FROM IMMUNOLOGICAL ANGLE
DrugPedia:
MycoTB: AN OPEN SOURCE SOFTWARE FOR MANAGING M. TUBERCULOSIS DATA
IN SILICO APPROACH
- SEARCHING POTENTIAL DRUG TARGETS, DESIGNING EFFECTIVE INHIBITORS, MANAGING AND ANNOTATING M. TUBERCULOSIS DATA
INVOLVEMENT OF PUBLIC AGAINST WAR
- OSDD IS A PLATFORM, C2DIS A EXPERIMENT TO INVOLVE STUDENTS, EFFECT USE OF PUBLIC IS CHALLENGE.
MANAGING AND SHARING OF DATA
-TRADITIONAL DBMS ARE RIGID, ANNOTATING PROBLEM IS NOT DEFINED PRBLEM, NEED OF FLEXIBLE DBMS (MycoTB)
DrugPedia PLATFORM FOR SHARING DATA.
CRDD: COMPUTATIONAL RESOURCE FOR DRUG DISCOVERY
C2D: ANNOTATING OF M.Tb PROTEOME FROM IMMUNOLOGICAL ANGLE
DrugPedia:
MycoTB: AN OPEN SOURCE SOFTWARE FOR MANAGING M. TUBERCULOSIS DATA
INDIA 800 FOUNDATION--
BUILDING ONE INDIA
INDIA HAS MADE HUGE ECONOMIC PROGRESS. HOWEVER THE NATURE OF THIS PROGRESS MASKS HUGE DISPARITIES IN DEVELOPMENT THAT MUST BE ADDRESSED.
WE LIVE IN A UN-PRECEDENTED,CONTRADISPLINARY ERA WHERE HUNGERS SOARS AMID RECORD HARVESTS; AND EXTREME POVERTY AND WEALTH EXIST ALONGSIDE ONE ANOTHER.
THE GREATEST CHALLENGE IS TO ERADICATE POVERTY AND STIMULATE SOCIAL JUSTICE.
THE GOVERNMENT HAS TO TAKE THE LEAD BY DEVELOPING AND INVESTING IN RURAL DEVELOPMENT. AGRICULTURE, EDUCATION AND HEALTH. INDIA800 AND CIVIC SOCIETY ORGANISATIONS HAVE KEY ROLE TO PLAY IN SHARING THEIR UNDERSTANDING OF WHAT WORKS AND WHAT DOES NOT.
THIS CAN ASSIST IN DEVELOPING INNOVATIVE SOLUTIONS, AND DELEIVERING KEY PROGRAMMES THAT ENSURE INCLUSIVITY.
INDIA HAS MADE HUGE ECONOMIC PROGRESS. HOWEVER THE NATURE OF THIS PROGRESS MASKS HUGE DISPARITIES IN DEVELOPMENT THAT MUST BE ADDRESSED.
WE LIVE IN A UN-PRECEDENTED,CONTRADISPLINARY ERA WHERE HUNGERS SOARS AMID RECORD HARVESTS; AND EXTREME POVERTY AND WEALTH EXIST ALONGSIDE ONE ANOTHER.
THE GREATEST CHALLENGE IS TO ERADICATE POVERTY AND STIMULATE SOCIAL JUSTICE.
THE GOVERNMENT HAS TO TAKE THE LEAD BY DEVELOPING AND INVESTING IN RURAL DEVELOPMENT. AGRICULTURE, EDUCATION AND HEALTH. INDIA800 AND CIVIC SOCIETY ORGANISATIONS HAVE KEY ROLE TO PLAY IN SHARING THEIR UNDERSTANDING OF WHAT WORKS AND WHAT DOES NOT.
THIS CAN ASSIST IN DEVELOPING INNOVATIVE SOLUTIONS, AND DELEIVERING KEY PROGRAMMES THAT ENSURE INCLUSIVITY.
SLX- ENABILING COLLABORATORIES--KRITHI NEELAKANTAN
The best talent lies outside of your organisation - Bill Joy (co-founder , sun)
Remember CPC? (collaborative product component)
shifthappens- Netcafe's law (as more people collaborate more robust task can easily be done with ease)
The Network is the Platform!
Social Networking
New Business Challenges: new workforce behaviour services> new communities> new expectations.
Rise of the Social Cysborg
Bottom line of social software: workforce productivity- transfer knowledge between & among workers- capture knowledge of exsting workers- employee engagement.
organisations are investing based on real, tangible returns.
Online Video has had a Particularly Strong Impact (e.g. youtube)
Sharing & Privacy Controls: channels-target content for a specific group of users
Privacy controls-
SLX evolution to address outcomes:
increase sales & marketing effectiveness; improve employee collaboration; deliver effective corporate communications; enhance training & learning
learning & KM+ HPC Services+data content repositories-- Services----- service creation tools-- common monitoring & management
Journal of Visualised Experiments
Remember CPC? (collaborative product component)
shifthappens- Netcafe's law (as more people collaborate more robust task can easily be done with ease)
The Network is the Platform!
Social Networking
New Business Challenges: new workforce behaviour services> new communities> new expectations.
Rise of the Social Cysborg
Bottom line of social software: workforce productivity- transfer knowledge between & among workers- capture knowledge of exsting workers- employee engagement.
organisations are investing based on real, tangible returns.
Online Video has had a Particularly Strong Impact (e.g. youtube)
Sharing & Privacy Controls: channels-target content for a specific group of users
Privacy controls-
SLX evolution to address outcomes:
increase sales & marketing effectiveness; improve employee collaboration; deliver effective corporate communications; enhance training & learning
learning & KM+ HPC Services+data content repositories-- Services----- service creation tools-- common monitoring & management
Journal of Visualised Experiments
COLLABORATIVE SCIENCE- JAIJIT BHATTACHARYYA
WHAT MACHINES DO?
WHAT NEXT GENERATION MACHINE DO?
SO, HOW DO YOU HARNESS MULTIPLE BRAIN POWER?
HOW WE DO CREATE SUPERBRAIN
TECHNOLOGY-WEB2.0
-PUBLIC HIGH PERFORMANCE COMPUTING -CLOUD - DIGITAL LIBRARIES-OPEN FORMATS
OpenCirrus
COLLABORATIVE INNOVATION FRAMEWORK
OPEN CONTENT-OPEN SOURCE (ACCESS TO DATA & CODE)-OPEN STANDARDS (ABILITY TO COLLABORATE)
PRINCIPLES OF MASSIVELY COLLABORATIVE SCIENCE:
COLLABORATION-COMMUNITY-SHARED OWNERSHIP OF KNOWLEDGE
PARADIGM SHIFT IN KNOWLEDGE CREATION:
INTELLECTUAL "PROPERTY"-
COLLABORATIVE SCIENCE-SHARE,COLLABORATE; COMMUNITY OWNED, ACCESSIBLE TO ALL; MODIFICATION ENCOURAGED
COLLABORATIVE DEVELOPMENT IN SOFTWARE
PATENT POLICIES: OPEN ACCESS TO PUBLIC FUNDED RESEARCH; OPEN ACCESS TO DATA; OPEN OPPURTUNITIES; COLLABORATIVE USAGE OF NON-DIGITED INFORMATION.
ECONOMIC IMPACT OF OPEN SOURCE SOFTWARE (i.e IT MEANS MANY THINGS).
WHAT NEXT GENERATION MACHINE DO?
SO, HOW DO YOU HARNESS MULTIPLE BRAIN POWER?
HOW WE DO CREATE SUPERBRAIN
TECHNOLOGY-WEB2.0
-PUBLIC HIGH PERFORMANCE COMPUTING -CLOUD - DIGITAL LIBRARIES-OPEN FORMATS
OpenCirrus
COLLABORATIVE INNOVATION FRAMEWORK
OPEN CONTENT-OPEN SOURCE (ACCESS TO DATA & CODE)-OPEN STANDARDS (ABILITY TO COLLABORATE)
PRINCIPLES OF MASSIVELY COLLABORATIVE SCIENCE:
COLLABORATION-COMMUNITY-SHARED OWNERSHIP OF KNOWLEDGE
PARADIGM SHIFT IN KNOWLEDGE CREATION:
INTELLECTUAL "PROPERTY"-
COLLABORATIVE SCIENCE-SHARE,COLLABORATE; COMMUNITY OWNED, ACCESSIBLE TO ALL; MODIFICATION ENCOURAGED
COLLABORATIVE DEVELOPMENT IN SOFTWARE
PATENT POLICIES: OPEN ACCESS TO PUBLIC FUNDED RESEARCH; OPEN ACCESS TO DATA; OPEN OPPURTUNITIES; COLLABORATIVE USAGE OF NON-DIGITED INFORMATION.
ECONOMIC IMPACT OF OPEN SOURCE SOFTWARE (i.e IT MEANS MANY THINGS).
Hiroaki Kitano & OSDD C2D Tuberculosis
Teen Murti Bhawan
01:02:00 PM
Map: the view of world
Google Map
EGF Receptor Cascade
Garuda Project (Vishnu ride)
oncology, CNS, Cardio, Infection- Garuda common Platform
Cell Designer-modelling tool
PAYAO: SBML Models Tagging System
Community Curation Platform- How to maintain Map?
Pathway Curation Suite-
why drug discovery is difficult?
Multiple genes cause many diseases.
Internet Router Topology - Human PPI
Robustness includes Homeostasis & Stability but not equal
Complete Robust System- cancer robustness-source of robustness-feedback loop within cell-
Intra Tumor Heterogeneity
Robustness Trade-offs
Robustness - Fragility
Bode Theorem
Collateral Sensitivity: Fragility Vs Resistance.
The conjecture- reduce cost & efficacy & sensitivity when two combination s of drug turn to cure other disease.
Open Pharma
Robustness - based target candidate selection, differential robustness
current question- which genes are over-expresing/mutant /missing in tumor cells?
computational fluid dynamics- big sucess-homogeous system
large network map-dynamic model construction- mechanism of AKT effect
the era of new drug design- what are problems, what need to be done, how to do it, we are crazy to mad the solution
01:02:00 PM
Map: the view of world
Google Map
EGF Receptor Cascade
Garuda Project (Vishnu ride)
oncology, CNS, Cardio, Infection- Garuda common Platform
Cell Designer-modelling tool
PAYAO: SBML Models Tagging System
Community Curation Platform- How to maintain Map?
Pathway Curation Suite-
why drug discovery is difficult?
Multiple genes cause many diseases.
Internet Router Topology - Human PPI
Robustness includes Homeostasis & Stability but not equal
Complete Robust System- cancer robustness-source of robustness-feedback loop within cell-
Intra Tumor Heterogeneity
Robustness Trade-offs
Robustness - Fragility
Bode Theorem
Collateral Sensitivity: Fragility Vs Resistance.
The conjecture- reduce cost & efficacy & sensitivity when two combination s of drug turn to cure other disease.
Open Pharma
Robustness - based target candidate selection, differential robustness
current question- which genes are over-expresing/mutant /missing in tumor cells?
computational fluid dynamics- big sucess-homogeous system
large network map-dynamic model construction- mechanism of AKT effect
the era of new drug design- what are problems, what need to be done, how to do it, we are crazy to mad the solution
Thursday, April 8, 2010
Conference: Day 1
TEEN MURTI BHAVAN
Time: 10:40:42 AM
OSDD-CONNECT2DECODE
Discussing about Tuberculosis:
Welcome note & History of Tuberculosis by Zakir Thomas.
How, Where & When about OSDD Tuberculosis Initaitive: S.K. Brahmachari
Inauguration note: Hon. Prithviraj Chauhan, Minister of State
"New Mind" make big things happen.
Time: 10:40:42 AM
OSDD-CONNECT2DECODE
Discussing about Tuberculosis:
Welcome note & History of Tuberculosis by Zakir Thomas.
How, Where & When about OSDD Tuberculosis Initaitive: S.K. Brahmachari
Inauguration note: Hon. Prithviraj Chauhan, Minister of State
"New Mind" make big things happen.
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