The document discusses the perspectives and opportunities of bioinformatics within the context of the bioeconomy. Specifically, it discusses: 1) Recent reports highlighting societal challenges that the bioeconomy and biotechnology can help address, such as health, resources, food security, and climate change adaptation. 2) Emerging disruptive technologies like next-generation genomics, synthetic biology, and their potential impacts on industries like healthcare, chemicals, food, and fuels. 3) The growing and rapidly expanding markets for synthetic biology and bioinformatics, projected to reach billions annually in coming years.

1. La Bioinformatica nelle prospettive della Bioeconomy
BIOSPACE REVOLUTION
‘Omics (Genomics and Beyond) Analytics & Modeling
Gaetano Scioscia
IBM Italia, Bari
BiP-Day 2013
Bari, 5 dicembre 2013
© 2013 IBM Corporation

2. La Bioinformatica nelle prospettive della Bioeconomy
Recent Reports in Bioeconomy: Biospace Revolution address
Societal Grand Challenges
“Biotechnology offers
technological solutions for
many of the health and
resource-based challenges
facing the world.”
© 2013 IBM Corporation
“The bioeconomy has emerged as
an Obama Administration priority
because of its tremendous potential
for growth as well as the many
other societal benefits it offers.”
“The mature, sustainable
Bioeconomy will help deliver
global food security, improve
nutrition and health, create smart
bio-based products and biofuels,
and help agriculture, forestry,
aquaculture and other ecosystems
to adapt to climate change.” 2
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3. La Bioinformatica nelle prospettive della Bioeconomy
Disruptive technologies: Advances
that will transform life, business,
and the global economy
May 2013
Next-generation genomics marries advances in the science of
sequencing and modifying genetic material with the latest big
data analytics capabilities. Today, a human genome can be
sequenced in a few hours and for a few thousand dollars, a task
that took 13 years and $2.7 billion to accomplish during the
Human Genome Project. … The next step is synthetic biology
—the ability to precisely customize organisms by “writing” DNA.
These advances in the power and availability of genetic science
could have profound impact on medicine, agriculture, and even
the production of high-value substances such as biofuels—as
well as speed up the process of drug discovery.
Insights for Industry Experts
• “Through all the ‘omics revolutions, essentially
turned biology into an Information Science”
• “We have massive amounts of information at the
top in the cloud, with users at the bottom in
different industries. The biggest barrier to any
real use is the lack of standardization and
connectability”
 Steve Burrill; July 8, 2013
 CEO,
 Burrill and Company
http://www.burrillandco.com/team-138G_Steven__Burrill.html
Range of sized potential
economic impacts
Low
• “In terms of industry investment, Healthcare,
Chemical, Food are hot targets; Fuel less so;
Electronics not interesting”
High
Estimated
potential
economic
impact of
technologies
in 2025
• “Huge value emerging in microbiome”
700B-1.6T (US$)
Next Generation Genomics
© 2013 IBM Corporation
Fast, low-cost gene
sequencing advanced big
data analytics, and synthetic
biology (“writing” DNA)
 Jonathan Fleming; July 11, 2013
 Managing General Partner,
 Oxford Bioscience
http://www.oxbio.com/team.html
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4. La Bioinformatica nelle prospettive della Bioeconomy
Biospace market is growing rapidly to a $11B in 2016
at a CAGR of 46%
The global value of the synthetic biology market* reached $1.1 billion in
2010. It is expected to reach $1.6 billion in 2011 and it will further grow
to $10.8 billion by 2016, increasing at a compound annual growth rate
(CAGR) of 45.8.%.
Source: BCC Research, Nov 2011
60
$49B
50
40
30
20
10
0
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
Bioinformatics market is $3.2 billion in 2012 and is forecasted to
grow to nearly $7.5 billion by 2017 with 20.3% CAGR. At this pace,
the market reaches at $13B in 2020.
Source: BCC Research, Mar 2013
*industries outside of Healthcare
© 2013 IBM Corporation
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5. La Bioinformatica nelle prospettive della Bioeconomy
Large companies across several industries have recently been
investing in Biospace
BP to Invest $500 Million on Biofuels at a Research Center
In one of the largest research grants by an oil company, BP is
planning to spend $500 million over the next 10 years to finance
major work on biofuels to find "longer-term commercial
alternatives to oil and gas."
Amyris rises on Sanofi malaria drug news
Amyris uses genetically modified microorganisms — mainly yeast —
to make products for a variety of markets including specialty
chemicals, fuels and fragrances. The company licensed its technology
to Sanofi in 2008 for use in making synthetic artemisinin. Sanofi
plans to make the medicine available at low cost
Nestlé to expand medical nutrition business
The Swiss-based food giant, Nestlé, has announced a major
initiative it claims will prevent and treat health conditions such as
diabetes, heart disease and obesity.
Nestlé says it will invest around $500 million over the next
decade in the sector. The firm said on Monday that it hopes to
"pioneer a new industry between food and pharma"
© 2013 IBM Corporation
DuPont brings deep pockets to Genencor purchase
In early January, DuPont announced it would acquire Danisco, parent
of Genencor, for $6.3 billion. Genencor represents 35 percent of
Danisco’s total sales.
BASF Plans Production of Butanediol From Renewable
Feedstock Using Genomatica Technology
BASF plans to begin production of 1,4-butanediol based on
renewable feedstock (renewable BDO) using the patented process
of Genomatica, San Diego, California. The one-step fermentation
process is based on sugars as a renewable feedstock.
Microbes that mine
The Sossego mine, which Vale opened in 2004, produced 109,000
tons of copper in 2011. Its tailings pond, where samples of fungi
and bacteria are collected, contains approximately 90 million tons
of 0.07% copper-grade detritus. If this entire mineral content were
recovered, Vale could earn gross receipts of approximately
US$1.4 billion, more than the entire US$1.2 billion the company
invested between 1997 and 2004 to make the mine operational.
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6. La Bioinformatica nelle prospettive della Bioeconomy
IBM Offering will Enhance the Value of the R&D Process, Through
Insight Discovery and Advanced Modeling and Simulation
- Building upon existing IBM investments in HCLS, Genomic Medicine-Cross Brand
Strategic Initiative
Potential strategic
partners
CLOUD OFFERING
API access to client
R&D environment
Insight extraction;
Reuse of previous
insights;
High value patents
Simulation &
Modeling
GBS lead virtual CRO (Contract Research Organization)
molecular modeling
systems biology
Design
Bio CAD
Analytics
machine learning
synthetic routes discovery
Watson
Aggregation,
Cleansing, Prep
Data
genome
© 2013 IBM Corporation
pathway
‘omics
literature phenotype
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7. La Bioinformatica nelle prospettive della Bioeconomy
Methodology for modeling biological (‘Omics)
systems leverages techniques from circuit design
Use case: efficient chemical production (such as butanol)
Specification
•Input (abundant chemicals)
•Output (desired chemicals)
•Performance
• Yield
• Throughput
• Stabilities
• Response time
Find Biosynthetic Routes to
meet specification from Big Data.
Input:
Glucose
Output:
Butanol
© 2013 IBM Corporation
Design
Predictive Modeling
Simulation
•Models (Systems Biology)
• ODE
• PDE
• SDE
• Agent Based
•Input Parameters
•Molecular Bioenzyme Models
Select parts/devices for the
candidate biosynthetic routes
using Bio CAD.
Perform a predictive modeling
and simulations to pick
promising candidates for
implementations using HPC.
•Chassis
• E. Coli, Yeast, Algae etc.
•Devices/Bioparts
• Promoters
• Ribosomal Binding Sites
• Genes
• Terminators
•Intracellular Interactions
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8. La Bioinformatica nelle prospettive della Bioeconomy
Predictive Modeling in Depth
Structure Activity Relationship
Input
Scoring
Activity (μmol/min-mg)
E. Coli Wild Type
35
13
His131Arg
43
240
Trp130His
38
108
His131Arg, Trp130His
All possible pathways are generated and
responsible enzymes are mapped from literature
and pathway databases.
Enzyme
52
780
Each specie can have a different sequence.
Enzyme E1.2
E. Coli
Yeast
…
CCAAAGCTTGGGCCTTTTCGTGA
CCAAACCAATGGCCTTTTCTTGA
Chemical 2
Enzyme E2.6
Enzyme E2.3
Optimize known
enzymes
Chemical 3
Enzyme E3.4
Chemical 6
Chemical 4
Enzyme E4.5
Chemical 5
Enzyme E5.7
No Enzyme or
Pathway Known
Perform de novo design using
Molecular Dynamic and QM/MM
hybrid methods
Output
© 2013 IBM Corporation
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9. La Bioinformatica nelle prospettive della Bioeconomy
Food/Nutrition – Client Feedback
Michael Brown, Director, BioSciences & Sweeteness and
Taste Research, Global R&D, Coca-Cola
-R&D annual spend $60-100M
- Interested in getting the computational insights, as it pertain to their
personalized nutrition strategy
- Consumer analytics in our stack may be very good added value
- Strong relationship with IBM and IBM Research
Harold Schmitz, Chief Scientific Officer, Mars
- Strong research and innovation pipeline in 3-5 years with profound impact,
some occurring already, in plant genomics for food products, and in petcare
and petfood products.
- Genomics research is a critical input to overall R&D of food products, for
example in the chocolate business, role of genomics is inextricably linked to
sustainable production of cocoa. In 3-5 years the supply chain will
increasingly be based on genomics. In 5-10 years it will mostly be genomics
based. Its impact is to large part of our chocolate business, in $Billions. not
give out such numbers.
- Mars already spends several $10Ms, with a positive slope for next 3-5 years.
- Partnerships are essential to compete with major food companies - Nestle,
Unilever. Serious partnerships with academic, govt labs, and few key
industrial research partners (e.g. IBM).
© 2013 IBM Corporation
Danone ® probiotic
yogurt for digestive
health and immune
system (Activia ®),
bone health (Densia ®)
and heart health
(Danacol ®).
Kellogg's®
Smart Start®
Strong Heart
Antioxidants
cereal
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10. La Bioinformatica nelle prospettive della Bioeconomy
Functional Processed Foods – A prototype use case
Client problem: Processed foods often have a negative impact on human health by adversely
altering the bacterial content of our intestinal tracts
Solution: Engineer foods with prebiotics to promote human health by promoting a healthy gut microbiome
IBM play: IT platform for modeling and simulating effects of food additives on gut microbial communities
Industry Differentiation: Systems biology domain experience, computational technology leadership
Processed food
Food engineering
(additives, prebiotics,
probiotics, fibers)
Simulate effect on
intestinal microbial
community
© 2013 IBM Corporation
Poor health
Obesity, diabetes, cardiovascular
disease, inflammatory bowel
disease, cancer, allergies,
osteoporosis
Client side
Analyze
food
chemistry
Design
product
Upload chemical
composition and
food assay results
API
Testing & iterative improvements
Measure substances of
interests: carcinogens,
cholesterol, vitamins, amino
acids, SCFA*
Data prep,
cleansing, and
aggregation
Systems
biology model
of gut
microbiology
Improved health
SCFA: Short Chain Fatty Acid
Test effect
on gut
microbes
Visual data analytics
Design
recommendations
Data analytics
and
visualization
(microbial
ratios, etc.)
Simulate food
effect on
microbial
content
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11. La Bioinformatica nelle prospettive della Bioeconomy
Energy/Biofuels
•Bioethanol and more
advanced biofuels such as
current infrastructure
compatible
butanol/isobutanol are
expected to grow rapidly.
•Oil Majors are investing
with synthetic biology
companies.
•36 Billion gallons in 2022
and 60 Billion gallons in
2030 (Obama: US objectives)
Specification
•Input: CO2
•Output Butanol
•Performance
• Low Cost
• High Throughput
• Continuous Process
• Minimum
Waste/Byproducts
© 2013 IBM Corporation
Design
•Chassis: Cyanobacteria
•Devices:
• Promoter Selection
• Optimized Codon
• Optimized Amino Acids
Predictive Modeling
•Models (Systems Biology) to
evaluate to find candidates for
implementation and measurements.
•Optimize enzymes through
structural biology modeling.
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12. La Bioinformatica nelle prospettive della Bioeconomy
Chemical Industry
•Currently over $7B worth of
chemicals are produced
biosynthetically and over $100B
in 2020 with CAGR 30%.
•10% of chemicals will be
produced in biorefineries in 2020
(World Economic Forum) and
25% will be by 2025 (US DOE
target)
•Not just bulk chemicals,
functional chemicals (enzymes,
drugs, tire rubber, polymer,
fragrance, OEL, OPV) will be
produced.
Specification
•Input: Glucose
•Output : Anti-Tuberculosis drug
•Performance
• Low Cost
• High product quality
• High yield
© 2013 IBM Corporation
Source: P. Nieuwenhuizen and D.
Lyon, J of Commercial Biotech., 2011
Design
•Chassis: E. Coli
•Devices:
• Promoter Selection
• Optimized Codon
• Optimized Amino Acids
Predictive Modeling
•Models (Systems Biology) to
evaluate to find candidates for
implementation and measurements.
•Optimize enzymes through
structural biology modeling.
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13. La Bioinformatica nelle prospettive della Bioeconomy
© 2013 IBM Corporation
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14. La Bioinformatica nelle prospettive della Bioeconomy
Backup
© 2013 IBM Corporation
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15. La Bioinformatica nelle prospettive della Bioeconomy
World Economic Forum: Top 10 Emerging Technologies 2012
1. Informatics for adding value to information
The quantity of information now available to individuals and organizations is unprecedented in human history, and the rate of information generation continues to grow exponentially.
Yet, the sheer volume of information is in danger of creating more noise than value, and as a result limiting its effective use. Innovations in how information is organized, mined and
processed hold the key to filtering out the noise and using the growing wealth of global information to address emerging challenges.
2. Synthetic biology and metabolic engineering
The natural world is a testament to the vast potential inherent in the genetic code at the core of all living organisms. Rapid advances in synthetic biology and metabolic engineering are
allowing biologists and engineers to tap into this potential in unprecedented ways, enabling the development of new biological processes and organisms that are designed to serve
specific purposes – whether converting biomass to chemicals, fuels and materials, producing new therapeutic drugs or protecting the body against harm.
3. Green Revolution 2.0 – technologies for increased food and biomass
Artificial fertilizers are one of the main achievements of modern chemistry, enabling unprecedented increases in crop production yield. Yet, the growing global demand for healthy and
nutritious food is threatening to outstrip energy, water and land resources. By integrating advances across the biological and physical sciences, the new green revolution holds the
promise of further increasing crop production yields, minimizing environmental impact, reducing energy and water dependence, and decreasing the carbon footprint.
4. Nanoscale design of materials
The increasing demand on natural resources requires unprecedented gains in efficiency. Nanostructured materials with tailored properties, designed and engineered at the molecular
scale, are already showing novel and unique features that will usher in the next clean energy revolution, reduce our dependence on depleting natural resources, and increase atomefficiency manufacturing and processing.
5. Systems biology and computational modelling/simulation of chemical and biological systems
For improved healthcare and bio-based manufacturing, it is essential to understand how biology and chemistry work together. Systems biology and computational modelling and
simulation are playing increasingly important roles in designing therapeutics, materials and processes that are highly efficient in achieving their design goals, while minimally impacting
on human health and the environment.
6. Utilization of carbon dioxide as a resource
Carbon is at the heart of all life on earth. Yet, managing carbon dioxide releases is one of the greatest social, political and economic challenges of our time. An emerging innovative
approach to carbon dioxide management involves transforming it from a liability to a resource. Novel catalysts, based on nanostructured materials, can potentially transform carbon
dioxide to high value hydrocarbons and other carbon-containing molecules, which could be used as new building blocks for the chemical industry as cleaner and more sustainable
alternatives to petrochemicals.
7. Wireless power
Society is deeply reliant on electrically powered devices. Yet, a significant limitation in their continued development and utility is the need to be attached to the electricity grid by wire –
either permanently or through frequent battery recharging. Emerging approaches to wireless power transmission will free electrical devices from having to be physically plugged in, and
are poised to have as significant an impact on personal electronics as Wi-Fi had on Internet use.
8. High energy density power systems
Better batteries are essential if the next generation of clean energy technologies are to be realized. A number of emerging technologies are coming together to lay the foundation for
advanced electrical energy storage and use, including the development of nanostructured electrodes, solid electrolysis and rapid-power delivery from novel supercapacitors based on
carbon-based nanomaterials. These technologies will provide the energy density and power needed to supercharge the next generation of clean energy technologies.
9. Personalized medicine, nutrition and disease prevention
As the global population exceeds 7 billion people – all hoping for a long and healthy life – conventional approaches to ensuring good health are becoming less and less tenable, spurred
on by growing demands, dwindling resources and increasing costs. Advances in areas such as genomics, proteomics and metabolomics are now opening up the possibility of tailoring
medicine, nutrition and disease prevention to the individual. Together with emerging technologies like synthetic biology and nanotechnology, they are laying the foundation for a
revolution in healthcare and well-being that will be less resource intensive and more targeted to individual needs.
10. Enhanced education technology
New approaches are needed to meet the challenge of educating a growing young population and providing the skills that are essential to the knowledge economy. This is especially the
case in today’s rapidly evolving and hyperconnected globalized society. Personalized IT-based approaches to education are emerging that allow learner-centred education, critical
thinking development and creativity. Rapid developments in social media, open courseware and ubiquitous access to the Internet are facilitating outside classroom and continuous
education.
© 2013 IBM Corporation
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16. La Bioinformatica nelle prospettive della Bioeconomy
Computer will accelerate Biospace Revolution
 Search space is enormous!
 Data
– Literature (unstructured)
– Genomic Data
• Millions of species on Earth
• Each specie has 1000s of gene
– Omics Data
• Mass-spec data
• Protein structure data (PDB etc.)
• Transcriptome data
• Pathway data (KEGG etc.)
– Chemical Data
• Almost infinite # of chemical compounds (only 10 M is known)
 Insight Discovery
– Biosynthetic Routes
– Effects of external stimulus
 Modeling/Simulation
– Multiple devices to design
– Order of devices matters
– Each device consists of promoter, RBS, gene
– Gene can be optimized
– Bioenzyme modeling and optimization through structural biology and computational chemistry
© 2013 IBM Corporation
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17. La Bioinformatica nelle prospettive della Bioeconomy
Example: Biosynthetic Pathways of Isobutanol
Enzyme
Glucose
Acetate synthase
•Each enzyme can have variations
between species. The sequence and
structure information can be carried
out to further optimization of activity.
•An alternative pathway might exist to
shortcut reactions. Either find such an
enzyme from known species or de
Novo design of enzyme is carried out.
Pyruvate
Acetyl-CoA
KARI
S-Acetolactate
Novel Enzymes
Acetohydroxy acid dehydratase
2,3-dihydroxy
isovalerate
Acetohydroxy acid dehydratase
Butyryl-CoA
Isobutyryl-CoA mutase
Isobutyryl-CoA
Acylating aldehide dehydrogenase
2-ketoisovalerate
Valine
dehydrogenase
Branched chain keto
acid dehydrogenase
Branched chain keto
Acid decarboxylase
Valine
Valine decarboxylase
Isobutylamine
Omega transaminase
Isobutylaldehyde
Branched chain alcohol dehydrogenase
Isobutanol
© 2013 IBM Corporation
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18. La Bioinformatica nelle prospettive della Bioeconomy
Solution Overview:
Application
Healthcare
•Personalized/Preventive/Preem
ptive Healthcare
•Early detection and better
Cancer Survival
•Programmed Cell Therapy
•Accelerated drug discovery
Agriculture and Food
•Improve food production
efficiency
•Expand arable land
•Food safety
•Artificial meat
Analytics
•Biofuel productions and
process innovations.
•Clean water, soil, and air by
bacteria and insects
•Recovery heavy metal,
precious metal and rare earth
•carbon sequestration
Biology Multimodal Big Data Analytics
Cognitive Computing
Statistical Analysis
•Watson
•Automatic Insight Discovery
Energy and Environment
Chemical, Pharmaceutical
and Consumer Products
•Green Chemistry
•High functional products
•Inexpensive manufacturing
in silico Design and Predictive Modeling
Systems Biology
Molecular Model
•QTL analysis
•Similarity
•Machine Learning
•Pathway Analysis
•Disease Modeling
•In-vitro Human/Animal Model
•Protein Modeling
•Compound Modeling
•Membrane
•Nucleic Acid Modeling
•Tissue
Data
Sequence Data
•DNA/Genome
•RNA
•Microbiome
•Immuno profile
•Epigenome
Technology Layer
$1000 Genome
© 2013 IBM Corporation
Other Omics
•Metabolomics
•Proteomics
•Gene Expression
Image
•Body Scan
•Brain scan
•Cell Image
•Virus
•Molecules
Sense and Interact with Biological Objects
Nanotechnology
•Microarray
•Non-invasive biosensor/MEMS
•Cell Machine Interface
•Micro-/Nanofluidics
•DDS (Drug Delivery System)
•Nanoscaffold/tissue engineering
•Advanced Microscopy
Sensor Data
•Virus/bacteria
•Toxic chemical
compounds
•vital
Text
•Literature
•Web
•Medical Records
Imaging Technology
•CT
•MRI/fMRI
•STED, STORM/PALM, SIM
•Confocal Microscopy
•Mass Spectrometr
•Crystallography
•Hi-C
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19. La Bioinformatica nelle prospettive della Bioeconomy
Paradigm Shift in Industry (New Industry Revolution)
US DOE set goal of at least 25% of renewable source for industrial
products in 2025 (25x25) and 30% of biofuel in 2030 (30x30).
Drivers of Biospace Revolution
Synthetic Biology
Before 1970
2000
Bioinformatics
Oil Parity Expected
circa 2020
coal
coal
Oil
Coalchemical
© 2013 IBM Corporation
Oil
Green
Chemical
Petrochemical
2030
coal
Oil
Green
Chemical
Nanotechnology
20-30%
Green Chemical
Petrochemical & Green Chemical
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