A non confidential corporate presentation of "Manteia Predictive Médicine" as of September 2003. Présents DNA colony sequencing resutls, instrument, DNA preparation for genotyping.
DNA colony massively parrallel sequencing ams98 presentationPascal Mayer
First public presentation of massively parallel sequencing proof of principle (DNA colony base-by-base sequencing).
“A very large scale, high throughput and low cost DNA sequencing method based on a new 2-dimensional DNA auto-patterning process”,P. Mayer, L. Farinelli, G. Matton, C. Adessi, G. Turcatti, J.J. Mermod, E. Kawashima, presented at the Fith International Automation in Mapping and DNA Sequencing Conference, St. Louis (MI,USA), October 7-10, 1998. Invited presentation (P. Mayer).
This document discusses the production of transgenic animals and plants. It describes three main methods for producing transgenic animals: DNA microinjection, retrovirus-mediated gene transfer, and embryonic stem cell-mediated gene transfer. It also discusses 11 methods for transforming plants, including Agrobacterium-mediated transformation, biolistic transformation, and floral dip transformation. Finally, it lists some beneficial traits that have been engineered in transgenic plants, such as stress tolerance, herbicide tolerance, and increased nutritional quality.
Genome editing uses engineered nucleases to make targeted changes to DNA. There are several methods for engineered nucleases: zinc finger nucleases (ZFNs) use zinc finger proteins fused to FokI nuclease; transcription activator-like effector nucleases (TALENs) use transcription activator-like effector proteins fused to FokI; meganucleases are naturally occurring enzymes; and CRISPR/Cas uses a bacterial adaptive immune system. These nucleases make double-stranded breaks that are repaired through non-homologous end joining or homology-directed repair, allowing changes like gene knockouts, insertions, or replacements. Examples showed using these methods in plants and animals. Each method
ỨNG DỤNG CHẨN ĐOÁN PHÂN TỬ TRONG NHÓM BỆNH UNG THƯ nataliej4
Molecular diagnostic tests play an important role in the management of non-small cell lung cancer (NSCLC). Mutations in the epidermal growth factor receptor (EGFR) gene are commonly detected in NSCLC, especially in Asian populations, and help guide targeted therapy decisions. The cobas® EGFR Mutation Test is an FDA-approved real-time PCR test that detects 42 mutations in EGFR exons 18, 19, 20 and 21 in tissue and plasma samples. It provides a semi-quantitative index to monitor changes in mutant circulating tumor DNA levels over time, aiding in NSCLC patient management. EGFR mutation testing is crucial for identifying patients eligible for EGFR tyrosine kinase inhibitors.
This document provides details about Bryce Gochin-Lyon's Bar Mitzvah ceremony that took place on April 5, 2014 at Temple Ramat Zion in Northridge, California. It includes the Torah and Haftarah portions that Bryce chanted, a list of the Torah blessings and those who received them, and messages from Bryce's fathers Grant and Russell expressing their pride and love for Bryce on this occasion.
DNA colony massively parrallel sequencing ams98 presentationPascal Mayer
First public presentation of massively parallel sequencing proof of principle (DNA colony base-by-base sequencing).
“A very large scale, high throughput and low cost DNA sequencing method based on a new 2-dimensional DNA auto-patterning process”,P. Mayer, L. Farinelli, G. Matton, C. Adessi, G. Turcatti, J.J. Mermod, E. Kawashima, presented at the Fith International Automation in Mapping and DNA Sequencing Conference, St. Louis (MI,USA), October 7-10, 1998. Invited presentation (P. Mayer).
This document discusses the production of transgenic animals and plants. It describes three main methods for producing transgenic animals: DNA microinjection, retrovirus-mediated gene transfer, and embryonic stem cell-mediated gene transfer. It also discusses 11 methods for transforming plants, including Agrobacterium-mediated transformation, biolistic transformation, and floral dip transformation. Finally, it lists some beneficial traits that have been engineered in transgenic plants, such as stress tolerance, herbicide tolerance, and increased nutritional quality.
Genome editing uses engineered nucleases to make targeted changes to DNA. There are several methods for engineered nucleases: zinc finger nucleases (ZFNs) use zinc finger proteins fused to FokI nuclease; transcription activator-like effector nucleases (TALENs) use transcription activator-like effector proteins fused to FokI; meganucleases are naturally occurring enzymes; and CRISPR/Cas uses a bacterial adaptive immune system. These nucleases make double-stranded breaks that are repaired through non-homologous end joining or homology-directed repair, allowing changes like gene knockouts, insertions, or replacements. Examples showed using these methods in plants and animals. Each method
ỨNG DỤNG CHẨN ĐOÁN PHÂN TỬ TRONG NHÓM BỆNH UNG THƯ nataliej4
Molecular diagnostic tests play an important role in the management of non-small cell lung cancer (NSCLC). Mutations in the epidermal growth factor receptor (EGFR) gene are commonly detected in NSCLC, especially in Asian populations, and help guide targeted therapy decisions. The cobas® EGFR Mutation Test is an FDA-approved real-time PCR test that detects 42 mutations in EGFR exons 18, 19, 20 and 21 in tissue and plasma samples. It provides a semi-quantitative index to monitor changes in mutant circulating tumor DNA levels over time, aiding in NSCLC patient management. EGFR mutation testing is crucial for identifying patients eligible for EGFR tyrosine kinase inhibitors.
This document provides details about Bryce Gochin-Lyon's Bar Mitzvah ceremony that took place on April 5, 2014 at Temple Ramat Zion in Northridge, California. It includes the Torah and Haftarah portions that Bryce chanted, a list of the Torah blessings and those who received them, and messages from Bryce's fathers Grant and Russell expressing their pride and love for Bryce on this occasion.
There are two main types of genetic association studies: pedigree-based methods and pedigree-independent methods. Pedigree-based methods include positional cloning and the founder gene approach which use linkage analysis and genetic mapping of families. Pedigree-independent methods include the candidate gene approach and genome-wide association studies which examine associations between genetic variants and phenotypes across many individuals.
A New Generation Of Mechanism-Based Biomarkers For The ClinicJoaquin Dopazo
The document discusses moving from single gene biomarkers to more functional, modular biomarkers for disease. It argues that most diseases are caused by combinations of variants affecting functional modules rather than single genes. The document proposes analyzing genomic data like SNPs and gene expression in the context of protein interaction networks and gene ontologies to better capture disease mechanisms and identify more informative biomarkers. Examples show how this approach can prioritize genes interacting with known disease genes and find enriched functional groups associated with diseases.
Digging into thousands of variants to find disease genes in Mendelian and com...Joaquin Dopazo
This document summarizes a presentation about using genomic technologies to enable precision medicine. It discusses:
1) Precision medicine requires a better understanding of phenotype-genotype relationships and incorporating genomics into diagnostics and treatment.
2) Exome sequencing has been used to study a variety of rare and common diseases, generating a knowledge database.
3) Analysis pipelines involve initial processing, variant calling, knowledge-based prioritization using databases, and heuristic filtering to generate candidate genes.
4) Local population databases can improve gene prioritization by providing more accurate frequency filters of common variants.
This document discusses clinical and consumer applications of microarrays and genotyping technologies. It provides an overview of genotyping and different technologies like PCR microarrays and SNP microarrays. It describes how microarrays are still useful despite the rise of sequencing due to their low cost, high throughput, and ability to test millions of markers. The document outlines several applications of microarrays like direct-to-consumer testing, pharmacogenetics, and clinical sequencing. It also discusses challenges and trends in these areas like global initiatives to increase genomic data sharing.
This document discusses various methods for single nucleotide polymorphism (SNP) analysis, including their principles, advantages, and disadvantages. It describes SNP genotyping techniques like RFLP-PCR, TaqMan assays, microarrays, Sanger sequencing, SNaPshot, and next-generation sequencing. The key aspects are accuracy, throughput, cost, and ability to detect both known and unknown SNPs. The document emphasizes choosing methods based on required information extraction and cost effectiveness.
Gene sequencing and tb – a new age approach.pptxShajahanPS
Whole genome sequencing is increasingly being used to diagnose drug-resistant tuberculosis. It can identify resistance across all anti-TB drugs through DNA sequencing of the entire TB genome. This overcomes limitations of other tests and provides personalized treatment by rapidly detecting mixed infections, co-infections, and heteroresistance. While expensive and technically complex, whole genome sequencing improves treatment outcomes and aids in prevention by better understanding transmission.
Molecular techniques for pathology research - MDX .pdfsabyabby
This document discusses molecular techniques used in pathology research such as PCR, microarrays, next generation sequencing, immunohistochemistry, ELISA, and Western blotting. It provides details on each technique including the basic principles, applications in research, and examples of uses in studies of gene expression, cancer, bone disease, and growth retardation. The learning outcomes are to understand these techniques and their uses in basic and clinical research.
Advances and Applications Enabled by Single Cell TechnologyQIAGEN
Over the past 5 years, single-cell genomics have become a powerful technology for studying small samples and rare cells, and for dissecting complex populations such as heterogeneous tumors. Single-cell technology is enabling many new insights into diverse research areas from oncology, immunology and microbiology to neuroscience, stem cell and developmental biology. This webinar introduces single-cell technology and summarizes the newest scientific applications in various research areas, all in the context of current literature.
A microarray is a laboratory tool used to detect the expression of thousands of genes at the same time. DNA microarrays are microscope slides that are printed with thousands of tiny spots in defined positions, with each spot containing a known DNA sequence or gene.
04 rencontres biomédicale LIR Philippe FroguelAssociation LIR
1. Advances in human genomics research have identified over 800 genetic loci associated with common diseases like type 2 diabetes through genome-wide association studies and candidate gene studies.
2. Further research has found that most type 2 diabetes genes identified play a role in pancreatic beta-cell function, and that both frequent and rare genetic variants contribute to disease risk.
3. Integrating human genomics with metabolic medicine offers advantages for personalized healthcare, including identifying new drug targets, predicting drug responses and side effects, improving clinical trial design, and enabling more optimized long-term patient care.
This document discusses single nucleotide polymorphisms (SNPs), which are single base variations in DNA sequences that occur in at least 1% of the population. SNPs can influence phenotypes and disease susceptibility. They are abundant and useful genetic markers. The document outlines how SNPs are identified through genome sequencing and mapped. SNP profiles are unique to each individual and can provide information about disease predispositions and drug responses. Techniques for detecting known and unknown SNPs are also discussed.
Web applications for rapid microbial taxonomy identification ExternalEvents
http://www.fao.org/about/meetings/wgs-on-food-safety-management/en/
Web applications for rapid microbial taxonomy identification. Presentation from the Technical Meeting on the impact of Whole Genome Sequencing (WGS) on food safety management -23-25 May 2016, Rome, Italy.
Sequencing-based genotyping assays bring genotyping and genomics research to a crossroads. CD Genomics, as an advanced genomics service provider, has equipped sequencing-based genotyping technologies as well as SNP array services for our global customers. We deliver SNP and SNV discovery, genotype screening, and subsequent association analysis results, dedicated to facilitating research in pharmacogenomics, molecular breeding, genetics, and more. https://www.cd-genomics.com/snp-microarray.html
A molecular marker is a fragment of DNA associated with a specific location in the genome that is used to identify a particular DNA sequence. An ideal molecular marker is highly polymorphic, codominantly inherited, frequently distributed throughout the genome, easy to detect, reproducible, and allows for easy exchange of data between laboratories. Molecular markers like SSRs have various applications including genetic diversity analysis, cultivar identification, phylogenetic analysis, gene mapping, marker-assisted selection, and sex determination in plants.
As increasing numbers of people choose to have their genomes sequenced and made available for research, more genomic data is available for analysis by machine learning approaches. Single Nucleotide Polymorphisms (SNPs) are known to be a major factor influencing many physical traits, diseases and other phenotypes. Using publicly available data and tools we predict phenotype from genotype using SNP data (1 to 2 million SNPs). We utilize data analysis and machine learning approaches only, no domain knowledge, so that our automated approach may be generally used to predict different phenotypes from genotype. In the first application of our method we predicted eye color with 87% accuracy.
Next generation sequencing (NGS) provides a high-throughput and cheaper alternative to DNA sequencing through massively parallel sequencing of millions of DNA fragments simultaneously. NGS can be used for target sequencing to identify disease-causing mutations, RNA sequencing to study entire transcriptomes, and has various applications in cancer research and treatment including identifying mutations that predict responses to immunotherapy. However, NGS also faces challenges like accurately sequencing regions with repeats and detecting fusion genes.
This document provides an introduction and overview of a refresher course in molecular biology and bioinformatics. The course aims to provide a solid introduction to molecular biology techniques and bioinformatics tools currently used to investigate molecular mechanisms and their application to disease diagnosis and treatment. It will introduce concepts like genomics, transcriptomics, proteomics, epigenetics, genome editing with CRISPR, molecular cloning, and genome-wide association studies. The course also discusses various molecular biology techniques like DNA sequencing, PCR, immunohistochemistry and their role in furthering our understanding of human disease at the molecular level to improve patient care through more accurate diagnosis and targeted therapies.
Professor Michael Levin's presentation at Meningitis Research Foundation's 2013 conference Meningitis & Septicaemia in Children & Adults www.meningitis.org/conference2013
Monitoring and Managing Anomaly Detection on OpenShift.pdfTosin Akinosho
Monitoring and Managing Anomaly Detection on OpenShift
Overview
Dive into the world of anomaly detection on edge devices with our comprehensive hands-on tutorial. This SlideShare presentation will guide you through the entire process, from data collection and model training to edge deployment and real-time monitoring. Perfect for those looking to implement robust anomaly detection systems on resource-constrained IoT/edge devices.
Key Topics Covered
1. Introduction to Anomaly Detection
- Understand the fundamentals of anomaly detection and its importance in identifying unusual behavior or failures in systems.
2. Understanding Edge (IoT)
- Learn about edge computing and IoT, and how they enable real-time data processing and decision-making at the source.
3. What is ArgoCD?
- Discover ArgoCD, a declarative, GitOps continuous delivery tool for Kubernetes, and its role in deploying applications on edge devices.
4. Deployment Using ArgoCD for Edge Devices
- Step-by-step guide on deploying anomaly detection models on edge devices using ArgoCD.
5. Introduction to Apache Kafka and S3
- Explore Apache Kafka for real-time data streaming and Amazon S3 for scalable storage solutions.
6. Viewing Kafka Messages in the Data Lake
- Learn how to view and analyze Kafka messages stored in a data lake for better insights.
7. What is Prometheus?
- Get to know Prometheus, an open-source monitoring and alerting toolkit, and its application in monitoring edge devices.
8. Monitoring Application Metrics with Prometheus
- Detailed instructions on setting up Prometheus to monitor the performance and health of your anomaly detection system.
9. What is Camel K?
- Introduction to Camel K, a lightweight integration framework built on Apache Camel, designed for Kubernetes.
10. Configuring Camel K Integrations for Data Pipelines
- Learn how to configure Camel K for seamless data pipeline integrations in your anomaly detection workflow.
11. What is a Jupyter Notebook?
- Overview of Jupyter Notebooks, an open-source web application for creating and sharing documents with live code, equations, visualizations, and narrative text.
12. Jupyter Notebooks with Code Examples
- Hands-on examples and code snippets in Jupyter Notebooks to help you implement and test anomaly detection models.
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There are two main types of genetic association studies: pedigree-based methods and pedigree-independent methods. Pedigree-based methods include positional cloning and the founder gene approach which use linkage analysis and genetic mapping of families. Pedigree-independent methods include the candidate gene approach and genome-wide association studies which examine associations between genetic variants and phenotypes across many individuals.
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The document discusses moving from single gene biomarkers to more functional, modular biomarkers for disease. It argues that most diseases are caused by combinations of variants affecting functional modules rather than single genes. The document proposes analyzing genomic data like SNPs and gene expression in the context of protein interaction networks and gene ontologies to better capture disease mechanisms and identify more informative biomarkers. Examples show how this approach can prioritize genes interacting with known disease genes and find enriched functional groups associated with diseases.
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This document discusses various methods for single nucleotide polymorphism (SNP) analysis, including their principles, advantages, and disadvantages. It describes SNP genotyping techniques like RFLP-PCR, TaqMan assays, microarrays, Sanger sequencing, SNaPshot, and next-generation sequencing. The key aspects are accuracy, throughput, cost, and ability to detect both known and unknown SNPs. The document emphasizes choosing methods based on required information extraction and cost effectiveness.
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Whole genome sequencing is increasingly being used to diagnose drug-resistant tuberculosis. It can identify resistance across all anti-TB drugs through DNA sequencing of the entire TB genome. This overcomes limitations of other tests and provides personalized treatment by rapidly detecting mixed infections, co-infections, and heteroresistance. While expensive and technically complex, whole genome sequencing improves treatment outcomes and aids in prevention by better understanding transmission.
Molecular techniques for pathology research - MDX .pdfsabyabby
This document discusses molecular techniques used in pathology research such as PCR, microarrays, next generation sequencing, immunohistochemistry, ELISA, and Western blotting. It provides details on each technique including the basic principles, applications in research, and examples of uses in studies of gene expression, cancer, bone disease, and growth retardation. The learning outcomes are to understand these techniques and their uses in basic and clinical research.
Advances and Applications Enabled by Single Cell TechnologyQIAGEN
Over the past 5 years, single-cell genomics have become a powerful technology for studying small samples and rare cells, and for dissecting complex populations such as heterogeneous tumors. Single-cell technology is enabling many new insights into diverse research areas from oncology, immunology and microbiology to neuroscience, stem cell and developmental biology. This webinar introduces single-cell technology and summarizes the newest scientific applications in various research areas, all in the context of current literature.
A microarray is a laboratory tool used to detect the expression of thousands of genes at the same time. DNA microarrays are microscope slides that are printed with thousands of tiny spots in defined positions, with each spot containing a known DNA sequence or gene.
04 rencontres biomédicale LIR Philippe FroguelAssociation LIR
1. Advances in human genomics research have identified over 800 genetic loci associated with common diseases like type 2 diabetes through genome-wide association studies and candidate gene studies.
2. Further research has found that most type 2 diabetes genes identified play a role in pancreatic beta-cell function, and that both frequent and rare genetic variants contribute to disease risk.
3. Integrating human genomics with metabolic medicine offers advantages for personalized healthcare, including identifying new drug targets, predicting drug responses and side effects, improving clinical trial design, and enabling more optimized long-term patient care.
This document discusses single nucleotide polymorphisms (SNPs), which are single base variations in DNA sequences that occur in at least 1% of the population. SNPs can influence phenotypes and disease susceptibility. They are abundant and useful genetic markers. The document outlines how SNPs are identified through genome sequencing and mapped. SNP profiles are unique to each individual and can provide information about disease predispositions and drug responses. Techniques for detecting known and unknown SNPs are also discussed.
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Web applications for rapid microbial taxonomy identification. Presentation from the Technical Meeting on the impact of Whole Genome Sequencing (WGS) on food safety management -23-25 May 2016, Rome, Italy.
Sequencing-based genotyping assays bring genotyping and genomics research to a crossroads. CD Genomics, as an advanced genomics service provider, has equipped sequencing-based genotyping technologies as well as SNP array services for our global customers. We deliver SNP and SNV discovery, genotype screening, and subsequent association analysis results, dedicated to facilitating research in pharmacogenomics, molecular breeding, genetics, and more. https://www.cd-genomics.com/snp-microarray.html
A molecular marker is a fragment of DNA associated with a specific location in the genome that is used to identify a particular DNA sequence. An ideal molecular marker is highly polymorphic, codominantly inherited, frequently distributed throughout the genome, easy to detect, reproducible, and allows for easy exchange of data between laboratories. Molecular markers like SSRs have various applications including genetic diversity analysis, cultivar identification, phylogenetic analysis, gene mapping, marker-assisted selection, and sex determination in plants.
As increasing numbers of people choose to have their genomes sequenced and made available for research, more genomic data is available for analysis by machine learning approaches. Single Nucleotide Polymorphisms (SNPs) are known to be a major factor influencing many physical traits, diseases and other phenotypes. Using publicly available data and tools we predict phenotype from genotype using SNP data (1 to 2 million SNPs). We utilize data analysis and machine learning approaches only, no domain knowledge, so that our automated approach may be generally used to predict different phenotypes from genotype. In the first application of our method we predicted eye color with 87% accuracy.
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Overview
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As part of the talk, we will consider the architectural strategies necessary for the development of highly loaded fintech solutions. We will focus on using queues and streaming to efficiently work and manage large amounts of data in real-time and to minimize latency.
We will focus special attention on the architectural patterns used in the design of the fintech system, microservices and event-driven architecture, which ensure scalability, fault tolerance, and consistency of the entire system.
This talk will cover ScyllaDB Architecture from the cluster-level view and zoom in on data distribution and internal node architecture. In the process, we will learn the secret sauce used to get ScyllaDB's high availability and superior performance. We will also touch on the upcoming changes to ScyllaDB architecture, moving to strongly consistent metadata and tablets.
Northern Engraving | Modern Metal Trim, Nameplates and Appliance PanelsNorthern Engraving
What began over 115 years ago as a supplier of precision gauges to the automotive industry has evolved into being an industry leader in the manufacture of product branding, automotive cockpit trim and decorative appliance trim. Value-added services include in-house Design, Engineering, Program Management, Test Lab and Tool Shops.
In the realm of cybersecurity, offensive security practices act as a critical shield. By simulating real-world attacks in a controlled environment, these techniques expose vulnerabilities before malicious actors can exploit them. This proactive approach allows manufacturers to identify and fix weaknesses, significantly enhancing system security.
This presentation delves into the development of a system designed to mimic Galileo's Open Service signal using software-defined radio (SDR) technology. We'll begin with a foundational overview of both Global Navigation Satellite Systems (GNSS) and the intricacies of digital signal processing.
The presentation culminates in a live demonstration. We'll showcase the manipulation of Galileo's Open Service pilot signal, simulating an attack on various software and hardware systems. This practical demonstration serves to highlight the potential consequences of unaddressed vulnerabilities, emphasizing the importance of offensive security practices in safeguarding critical infrastructure.
3. Tomorrow:
Patient DNA is fully genotyped one time only
A database is consulted in order to
oDevelop a molecular diagnosis of specific disease
oPredict responses to each of the available treatmentsDiagnosis and treatment
Today’s medical practice is for the most part:
Imprecise in diagnosis
Selecting treatment by trial-and-error
4. Tomorrow: the Personal Genome Card is available.
The database is consulted whenever necessary
oGenetic susceptibility to specific diseases is assessed
Preventive measures are taken in consultation with a family physician, including:
oLife style changes
oRoutine screenings for those at elevated risk, allowing for early diagnosis and better prognosis
oPersonalized preventive treatment
Today’s medical practice is for the most part reactive to diseasePrevention
5. Bridging the gap
Need to decipher the genetic basis of common complex diseases and responses to treatment
Today’s technologies are not up to the task:
Too complex (e.g., procedures are SNP specific)
Too expensive (> 0.1€per SNP)
6. Drug Responses are Multigenic
Pharmacokinetics Pharmacodynamics
individual
metabolism
individual
action
Molecular sub-types
Drug Individual responses
individual
pathways
Individual response to medicines is likely a
consequence of many low-effect genetic variants
7. sporadic
Combinations of many low-effect
gene variants
(eg: AD, Migraine, NID- Diabetes, Psoriasis)
Most disease is the result of combinations of low- effect genetic variantsCommon Diseases are Multigenicfamilial
Moderate-penetrance
gene variants
(eg: BRCA1,2)
Single high- penetrance
gene variants
(eg: CF, Huntington Disease)
8. ABCDEFG
ABCDEFG ABCDEFG
ABCDEFG ABCDEFG
ABCDEFG ABCDEFG ABCDEFG ABCDEFG
Over Generations
A combination of many subtle
genetic variants may tip the balance
in favor of disease
ABCDEFG ABCDEFG
Combinations of low-effect variants
9. Finding low effect variants will require high density genotyping of large populations
“…a density of SNPs of one every 10,000 –30,000 bp can rapidly narrow the search for susceptibility genes*.” Roses. Nature, 405 (2000) pp862. (SVP, Genetics Research, GSK)
“…roughly 500,000 SNPs will be required for whole-genome association studies in samples drawn from large outbred populations.” (pp139). “…efficient technologies are needed for genotyping hundreds of thousands of SNPs in thousands of individuals” (pp143). Kruglyak. Nature Genetics, 22 (1999).(Fred Hutchinson Cancer Research Center & HHMI)
*100,000 –300,000 SNPs
10. Multigenic Diseases: Gene Hunting
Genome-wide / hypothesis-free approach
Using very high density markers
At least 300,000 SNPs/genome
Large numbers of subjects
At least 2,000 per disease/treatment
Totaling at least 600 million SNPs typed/disease
Today cost/SNP = 10-20¢
Tractable when cost falls below 1¢/SNP
12. SNPtyping with Manteia technology
No SNP map needed
Not SNP-specific
“One” tube per patient
Readily scalable
Detection method: sequencing genome fragments
Below 0.1¢ per SNP
13. Manteia Technology: PAS( Parallel Amplification and Sequencing )
Four basic steps
1: Isolate genomic DNA from blood or cheek-swab
2: Cut up the DNA and collect the fragments
3: Amplify all the fragments in parallel on a solid surface
4: Sequence all the fragments in parallel
14. Patient 1
Patient n
Isolate
Genomic DNA
Cut DNA with
Restriction Endonuclease Enzyme
1
2
3
4
5
1
2
3
4
5
15. Type IIs
recognition site
n
Genomicfragment
n
Ligation
Type IIs
digest
Short genomic
fragment
n
Linker 1
16. Restriction site
Type IIs
recognition sites
n
Genomicfragment
n
Ligation
n
Type IIs
digest
Short genomic
fragmentsPAS2
17. n
n
Ligation
Linearized
Colony Template
Linker 2
5
4
3
2
1
DNA fragment sizes
normalized
Each restriction endonuclease=> ~1.5 million fragments
18. 5
4
3
2
1
Clone DNA fragments
Into “DNA Colony Vectors”
5
4
3
2
1
DNA fragment sizes
normalized
n
Variable region
Constant region
Constant region
19. n
Colony vectors
Short primers
n
n
Functionalization
Chemically functionalized surface
20. PAS Array
Density = f([template],[primer],t)
ss DNA Colony Vector(107/cm2)
ss Oligonucleotide
Primers (4x104/μm2)
Glass surface
1
2
5’ endscovalently attached
3’ endsfree in solution
23. 1-2 μm
DNA
Colonies
(1000-2000 copies in each)
1
2
100 μm
24. Sequencing primers
Added to the array
DNA:DNA
Hybrids
C
A
C
T
G
C
T
G
A
Sequencing primer
Anonymous
Fragment of genomic
DNA (Variable region)
Colony Vector (Constant region)
Colony Vector (Constant region)
25. Cycle 3
C
A
C
T
G
C
T
G
A
G
T
0
1
2
3
4
Signal
A
G
T
C
C
A
C
T
G
C
T
G
A
A
0
1
2
3
4
Signal
A
G
T
C
Cycle 1
Wash
Add
C
A
C
T
G
C
T
G
A
Cycle 2
G
0
1
2
3
4
Signal
A
G
T
C
30. Genetic variability in the human population:
Between 2 individuals: 1 SNP every 1331 bp
(SNP consortium, Nature 409,928)
In the population (Krugliak, Nature Genetics 27,234 ):
Frequency >= 10% : 1 SNP every 600bp
Frequency >= 1% : 1 SNP every 290bp
Frequency >= 0.1%: 1 SNP every 200 bp
31. The same stretches of DNA are sequenced in each patient
patient #1
patient #47
patient #125
patient #571
....
....
Sequenced fragments
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
acgtaggtgcaggtcagt
…
tagcgtAtcgtaggtagat
tagcgtAtcgtaggtagat
tagcgtAtcgtaggtagat
tagcgtAtcgtaggtagat
tagcgtGtcgtaggtagat
tagcgtAtcgtaggtagat
tagcgtAtcgtaggtagat
tagcgtAtcgtaggtagat
tagcgtGtcgtaggtagat
tagcgtAtcgtaggtagat
…
SNP
Making SNP identification possible
Each restriction endonuclease: => 1.5 million fragments
=> 25 million bases sequenced
=> 1% of the genome scanned
=> 100,000 SNPs scored
32. Mega-SNP data analysis: “genetic” approach
Classical frequent SNP problem:
-number SNP >> population
-distance between SNP > linkage range
-moderate population (50~300)
=> How to differentiate real linkage signal from false positives/negatives
Manteia’s Mega-SNP approach:
-distance between SNP < linkage range
-moderately frequent SNPs
-large population (1,000~10,000)
=>SNP clusters of high statistical signifcance
1 Mbp
Linkage
Signal
1 Mbp
Linkage
Signal
2~4 LD range
“running average”
33. SNPtyping with Manteia technology
No dependent on SNP maps
Not SNP-specific
“One” tube per patient
Readily scalable
Detection method: sequencing genome fragments
Tracktable biostatistics and bioinformatics
Below 0.1¢ per SNP (Q1-2006)
34. Business Model
Identify Gene Variant Associations
Alone or in partnerships
Retain rights to these associations for application to:
Therapeutic response prediction
Disease risk assessments
License out rights for application to:
Drug discovery
Develop and market a Personal Genome Card in conjunction with access to a database of clinical and genetic associations.
35. Collaborations with biopharmaceutical companies
Clinical partnerships
Clinical trials assessment & recruitment
Drug revival
Development of marketed Companion Tests
Discovery partnerships
Target discovery in diseased populations
Transcriptome analysisCollaborations
36. Collaborations
Clinical
Studies
Association Studies
Gene Variants
Disease
Causation
Progression
Drug Targets
Response to Therapy
Drug Discovery
Predictive Tests
Marketing
Manteia
Technology
Individual
Patterns
37. Personal Genome Card
Internal Programs:
Personal Treatment Guidelines
In conjunction with Personal Genome Cards
Predict patient responses to therapy
Efficacy and side-effects
Personal Risk Profiles
In conjunction with Personal Genome Cards
Predict lifetime risk of sporadic cases of common diseases.
Permit appropriate interventions and monitoring for those at risk. Business Model
38. Treatment Guidelines
Single Disease Clinical Populations
Association Studies
Patterns ofGene Variants
Manteia
Technology
Therapy 1
Responders
Non
Responders
Therapy 2
Responders
Non
Responders
Therapy 3
Responders
Non
Responders
Pharmacokinetics
Pharmacodynamics
Disease subgrouping
Genotypes
Personal
Genotype
Card
Treatment
Guideline
PRODUCT
39. Disease Selection
Serious diseases
High incidence
Several treatments available
Each treatments works for only a fraction of patients
Treatments are expensive
Treatments have serious side effects
Delaying effective treatments leads to poorer prognosis
All frequent diseases where sub-optimal treatment has a high cost
40. Personal Treatment Guidelines
Market example: Breast Cancer
200,000 new diagnoses each year in US; 300,000 in EU.
$2,500 per comprehensive Treatment Guideline
Potential US+EU market: $1.25B/year
Maximal penetration @ 30% = $375MM/year
Net income @ 20% = $75MM/year
Personal Genome Card
41. Risk Profiles
Association Studies
Patterns ofGene Variants
Manteia
Technology
Genotypes
Personal
Genotype
Card
Risk Profile
PRODUCT
Single Disease Clinical Populations
Disease
Subgroups
Matched Populations
42. Disease Selection
High incidence
Prevention is possible
Preventive treatment is available
Early diagnosis leads to much better prognosis
Where there is either no available screen
Where screening is expensive or unpleasant
43. Personal Risk Profiles
Market example: Colorectal cancer
4,000,000 turn 50 each year in the US
8,000,000 target population US+EU
$500 Risk Profile for colorectal cancers
Potential US+EU market: $4B per year
Maximal penetration @ 10% = $400MM/year
Net income @ 10% = $40MM/year
Personal Genome Card