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BioMEMS The Market aspects of Oligonucleotide-Chips, Products, Applications and Competition, January 21, 2016

Posted in 3D Printing for Medical Application, Big Data, Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Informatics, Cell Biology, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Commercialization, Computational Biology/Systems and Bioinformatics, CRISPR/Cas9 & Gene Editing, Digital HealthCare – biotech & internet joint ventures, DNA repair, Exosomes, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Genetics & Pharmaceutical, Genome Biology, Genomic Expression, Genomic Testing: Methodology for Diagnosis, Intelligent Information Systems, MEMS, Mutagenesis, Proteosome, tagged DNA Sequencing, gene expression, genetics, genome, genomics, Proteomics, qPCR & SNP Genotyping Custom Oligonucleotides - highly sophisticated oligonucleotides - simple PCR primers Oligos in Plates RNA FISH, RNA, THERMO SCIENTIFIC APPLIED BIOSYSTEMS INVITROGEN FISHER SCIENTIFIC UNITY LAB SERVICES on February 2, 2016| Leave a Comment »

BioMEMS The Market aspects of Oligonucleotide-Chips, Products and Applications, Competition, January 21, 2016

Curator: Gérard LOISEAU, ESQ

BioMEMS

The Market aspects of Oligonucleotide-Chips, Products, Applications, Competition

January 21, 2016

2015-2020

The oligonucleotide synthesis market is expected to reach USD 1.918.6Billion at a CAGR of 10.1% by 2020 from USD 1.078.1Billion in 2015.

SOURCE

MARKETSANDMARKETS marketsandmarkets.com/

PLAYERS

Agilent Technologies Inc.
BioAutomation Corp.
Biosearch Technologies
Gen9 Inc.
GenScript Inc.
Illumina Inc.
Integrated DNA Technologies
New England Biolabs Inc.
Nitto Denko Avecia Inc.
OriGene Technologies Inc.
Sigma-Aldrich Corporation
Thermo Fisher Scientific Inc.
TriLink Biotechnologies

Agilent Technologies  CA NYSE :A 

http://www.agilent.com/

Agilent was created as a spin off from Hewlett-Packard Company in 1999.
Agilent Technologies Inc. is engaged in the life sciences, diagnostics and applied chemical markets. The Company provides application focused solutions that include instruments, software, services and consumables for the entire laboratory workflow. The Company has three business segments:

the life sciences and applied markets business,

the diagnostics and genomics business, and

the Agilent Cross Lab business

The Company’s life sciences and applied markets business segment brings together the Company’s analytical laboratory instrumentation and informatics.
The Company’s diagnostics and genomics business segment consists of three businesses: the Dako business, the genomics business and the nucleic acid solutions business.
The Company’s Agilent Cross Lab business segment combines its analytical laboratory services and consumables business

SOURCE

http://reuters.com/

PRODUCTS AND SERVICES

https://www.agilent.com/en-us/default#collapse-0

October 09, 2015 03:21 PM Eastern Daylight Time
CARPINTERIA, Calif.–(BUSINESS WIRE)–Dako, an Agilent Technologies company and a worldwide provider of cancer diagnostics, today announced the U.S. Food and Drug Administration has approved a new test that can identify PD-L1 expression levels on the surface of non-small cell lung cancer tumor cells and provide information on the survival benefit with OPDIVO^® (nivolumab) for patients with non-squamous NSCLC.

SOURCE

BUSINESS WIRE busibesswire.com/

BioAutomation Corp.   TX 

http://bioautomation.com/

PRODUCTS AND SERVICES

DNA and RNA synthesis reagents for the MerMades

Note: The MerMade 192E Oligonucleotide synthesizer is designed to synthesize DNA, RNA & LNA oligonucleotides in a column format

PARTNERSHIPS

HONGENE BIOTECH : BIOAUTOMATION is the exclusive distributor for the Americas
EMD MILLIPORE
BIOSEARCH TECHNOLOGIES

DISTRIBUTORS

LINK TECHNOLOGIES : UK
AME BIOSCIENCE : UK
BOSUNG SCIENCE : KOREA
DNA CHEM : CHINA
WAKO : JAPAN
ACE PROBE : INDIA

SOURCE

bioautomation.com/

Biosearch Technologies  CA 

http://biosearchtech.com/

PRODUCTS

qPCR & SNP Genotyping
Custom Oligonucleotides
– highly sophisticated oligonucleotides
– simple PCR primers
Oligos in Plates
RNA FISH
Synthesis Reagents
Immunochemicals
Primers
Probes
Large-Scale Synthesis Oligos
Intermediate-Scale Synthesis Oligos

SERVICES

GMP & Commercial Services
OEM & Kit Manufacturing
qPCR Design Collaborations

DISTRIBUTORS

SOURCE

biosearchtech.com/

Gen9 Inc.  MA  

http://www.gen9bio.com/

PRODUCTS

Gen9 is building on advances in synthetic biology to power a scalable fabrication capability that will significantly increase the world’s capacity to produce DNA content. The privately held company’s next-generation gene synthesis technology allows for the high-throughput, automated production of DNA constructs at lower cost and higher accuracy than previous methods on the market. Founded by world leaders in synthetic biology, Gen9 aims to ensure the constructive application of synthetic biology in industries ranging from enzyme and chemical production to pharmaceuticals and biofuels.

SERVICES

Synthetic Biology
Gene Synthesis Services
Variant Libraries
Gene Sequence Design Services

INVESTORS

Agilent Technologies : Private Equity
CAMBRIDGE, Mass. and SANTA CLARA, Calif. — April 24, 2013 —Gen9 Receives $21 Million Strategic Investment from Agilent Technologies

SOURCE

gen9bio.com/

GenScript Inc.  NJ  

http://www.genscript.com/

GenScript is the largest gene synthesis provider in the USA

GenScript Corporation, a biology contract research organization, provides biological research and drug discovery services to pharmaceutical companies, biotech firms, and research institutions in the United States, Europe, and Japan. It offers bio-reagent, custom molecular biology, custom peptide, protein production, custom antibody production, drug candidates testing, assay development and screening, lead optimization, antibody drug development, gene synthesis, and assay-ready cell line production services.

The company also offers molecular biology, peptide, protein, immunoassay, chemicals, and cell biology products. It offers its products through distributors in Tokyo, Japan; and Seoul, Korea. GenScript Corporation has a strategic partnership with Immunologix, Inc. The company was founded in 2002 and is based in Piscataway, New Jersey. It has subsidiaries in France, Japan, and China.

Note: As of October 24, 2011, Immunologix, Inc. was acquired by Intrexon Corporation. Immunologix, Inc. develops and produces antibody-based therapeutics for various biological targets. It produces human monoclonal antibodies against viral, bacterial, and tumor antigens, as well as human auto antigens.

Intrexon Corporation, founded in 1998, is a leader in synthetic biology focused on collaborating with companies in Health, Food, Energy, Environment and Consumer sectors to create biologically based products that improve quality of life and the health of the planet.

PRODUCTS AND SERVICES

Gene synthesis
Antibody services
Protein Services
Peptide services

INVESTORS 

Note: The Balloch Group (‘TBG’) was established in 2001 by Howard Balloch (Canada‘s ambassador to China from 1996 to 2001). TBG has since grown from a market-entry consultancy working with North American clients in China to a leading advisory and merchant banking firm serving both domestic Chinese companies and multinational corporations. TBG was ranked as the number one boutique investment bank in China by ChinaVenture in 2008.

Kleiner, Perkins, Caufield and Byers

Illumina Inc. CA 

http://illumina.com/

Monica Heger : SAN FRANCISCO (GenomeWeb) – Illumina today announced two new next-generation sequencing platforms, a targeted sequencing system called MiniSeq and a semiconductor sequencer that is still under development.

Illumina disclosed the initiatives during a presentation at the JP Morgan Healthcare conference held here today. During the presentation, Illumina CEO Jay Flatley also announced a new genotyping array called Infinium XT; a partnership with Bio-Rad to develop a single-cell sequencing workflow; preliminary estimates of its fourth-quarter 2015 revenues; and an update on existing products. The presentation followed the company’s announcement on Sunday that it has launched a new company called Grail to develop a next-generation sequencing test for early cancer detection from patient blood samples.

The MiniSeq system, which is based on Illumina’s current sequencing technology, will begin shipping early this quarter and has a list price of $49,500. It can perform a variety of targeted DNA and RNA applications, from single-gene to pathway sequencing, and promises “all-in” prices, including library prep and sequencing, of $200 to $300 per sample, Flatley said during the JP Morgan presentation.

SOURCES

https://www.genomeweb.com/sequencing-technology/illumina-unveils-mini-targeted-sequencer-semiconductor-sequencing-project-jp

http://investor.biospace.com/biospace/quote?Symbol=ILMN

PRODUCTS AND SERVICES

Mid to large scale manufacturing assets
Analytical Labs
Pre-clinical
Clinical
Launched products

COMPETITORS

https://finance.yahoo.com/q/co?s=ILMN+Competitors Tue, Feb 2, 2016, 2:16pm EST – US Markets

	ILMN	PVT1	AFFX	LMNX	Industry
Market Cap:	22.75B	N/A	1.13B	835.66M	134.14M
Employees:	3,700	10,000	1,200	745	45.00
Qtrly Rev Growth (yoy):	0.14	N/A	-0.01	0.07	0.18
Revenue (ttm):	2.14B	3.80B¹	357.74M	235.37M	8.47M
Gross Margin (ttm):	0.73	N/A	0.63	0.71	0.58
EBITDA (ttm):	770.84M	N/A	46.64M	52.99M	-12.31M
Operating Margin (ttm):	0.30	N/A	0.08	0.17	-1.62
Net Income (ttm):	510.36M	430.90M¹	11.22M	39.29M	N/A
EPS (ttm):	3.42	N/A	0.13	0.93	-0.34
P/E (ttm):	45.43	N/A	104.40	20.91	25.33
PEG (5 yr expected):	2.68	N/A	4.66	0.55	N/A
P/S (ttm):	10.87	N/A	3.13	3.45	13.65

Pvt1 = Life Technologies Corporation (privately held)

AFFX = Affymetrix Inc.

LMNX = Luminex Corporation

Integrated DNA Technologies (IDT) IOWA + CA

http://www.com/

Integrated DNA Technologies, Inc. (IDT), the global leader in nucleic acid synthesis, serving all areas of life sciences research and development, offers products for a broad range of genomics applications. IDT’s primary business is the production of custom, synthetic nucleic acids for molecular biology applications, including qPCR, sequencing, synthetic biology, and functional genomics. The company manufactures and ships an average of 44,000 custom nucleic acids per day to more than 82,000 customers worldwide. For more information, visit idtdna.com.

PRODUCTS AND SERVICES

https://eu.idtdna.com/site

DNA & RNA Synthesis
Custom DNA Oligos 96- & 384-Well Plates Ultramer Oligos Custom RNA Oligos SameDay Oligos HotPlates ReadyMade Primers Oligo Modifications Freedom
Dyes GMP for Molecular Diagnostics Large Scale Oligo Synthesis

Note : Skokie, IL – December 1, 2015. Integrated DNA Technologies Inc. (“IDT”), the global leader in custom nucleic acid synthesis, has entered into a definitive agreement to acquire the oligonucleotide synthesis business of AITbiotech Pte. Ltd. in Singapore (“AITbiotech”). With this acquisition, IDT expands its customer base across Southeast Asia making it possible for these additional customers to now have access to its broad range of products for genomic applications. AITbiotech will continue operations in its other core business areas.

New England Biolabs Inc.  MA  

http://www.neb.com/

PRODUCTS AND SERVICES

Restriction Endonucleases
PCR, Polymerases & Amplification Technologies
DNA Modifying Enzymes
Library Preparation for Next Generation Sequencing
Nucleic Acid Purification
Markers & Ladders

RNA Reagents
Gene Expression
Cellular Analysis

SOURCE

neb.com/

Nitto Denko Avecia Inc.  MA 

http://avecia.com/

With over 20 years of experience in oligonucleotide development and production, and over 1000 sequences manufactured, Avecia has played an integral role in the advancing oligo therapeutic market. Our mission is to continue to build value for our customers, as they progress through drug development into commercialization. And as a member of the Nitto Denko Corporation (nitto.com), Avecia is committed to the future of the oligonucleotide market. We are driven by innovative ideas and flexible solutions, designed to provide our customers with the best in service, quality, and technology.

SOURCE

http://avecia.com/

Note : 1918 Nitto Electric Industrial Co., Ltd. forms in Ohsaki, Tokyo, to produce electrical insulating materials in Japan.

2011 Acquires Avecia Biotechnology Inc. in the U.S.A.

OriGene Technologies Inc.  CA

http://www.com/

OriGene Technologies, Inc. develops, manufactures, and sells genome wide research and diagnostic products for pharmaceutical, biotechnology, and academic research applications. The company offers cDNA clones, including TrueORF cDNA, viral ORF, destination vectors, TrueClones (human), TrueClones (mouse), organelle marker plasmids, MicroRNA tools, mutant and variant clones, plasmid purification kits, transfection reagents, and gene synthesis service; and HuSH shRNA, siRNA, miRNA, qPCR reagents, plasmid purification products, transfection reagents, PolyA+ and total RNA products, first-strand cDNA synthesis, and CRISPR/Cas9 genome products. It also provides proteins and lysates, such as purified human proteins, over-expression cell lysates, mass spectrometry standard proteins, and protein purification reagents; UltraMAB IHC antibodies, TrueMAB primary antibodies, anti-tag and fluorescent proteins, ELISA antibodies, luminex antibodies, secondary antibodies, and controls and others; and anatomic pathology products, including IHC antibodies, detection systems, and IHC accessories

The company offers luminex and ELISA antibody pairs, autoantibody profiling arrays, ELISA kits, cell assay kits, assay reagents, custom development, and fluorogenic cell assays; TissueFocus search tools; tissue sections; tissue microarrays, cancer protein lysate arrays, TissueScan cDNA arrays, tissue blocks, and quality control products, as well as tissue RNA, DNA, and protein lysates; and lab essentials. Its research areas include cancer biomarker research, RNAi, pathology IHC, stem cell research, ion channels, and protein kinase products. The company provides gene synthesis and molecular biology services, genome editing, custom cloning, custom shRNA, purified protein, monoclonal antibody development, and assay development. It sells its products through distributors worldwide, as well as online. OriGene Technologies, Inc. was incorporated in 1995 and is based in Rockville, Maryland.

SOURCE

http://BLOOMBERG.com

PRODUCTS AND SERVICES

cDNA Clones Human, mouse, rat Expression validated
RNAi shRNA, siRNA microRNA & 3’UTR clones
Gene Synthesis Codon optimization Variant libraries
Real-time PCR Primer pairs, panels SYBR green reagents
Lab Essentials DNA/RNA purification kits Transfection reagents
Anatomic Pathology UltraMAB antibodies Specificity validated
Recombinant Proteins 10,000 human proteins from mammalian system
Antibodies TrueMAB primary antibodies Anti-tag antibodies
Assays and Kits ELISA & Luminex antibodies Autoantibody Profiling Array
Cancer & Normal Tissues Pathologist verified gDNA, RNA, sections, arrays

SOURCE

origene.com/

Sigma-Aldrich Corporation  MI  

http://www.sigmaaldrich.com/

Louis, MO – November 18, 2015 Merck KGaA, Darmstadt, Germany, Completes Sigma-Aldrich Acquisition

Merck KGaA today announced the completion of its $17 billion acquisition of Sigma-Aldrich, creating one of the leaders in the $130 billion global industry to help solve the toughest problems in life science.

Press Release: 18-Nov-2015

Letter to our Life Science Customers from Dr. Udit Batra

The life science business of Merck KGaA, Darmstadt, Germany brings together the world-class products and services, innovative capabilities and exceptional talent of EMD Millipore and Sigma-Aldrich to create a global leader in the life science industry.

“Everything we do starts with our shared purpose – to solve the toughest problems in life science by collaborating with the global scientific community.

This combination is built on complementary strengths, which will enable us to serve you even better as one organization than either company could alone.

This means providing a broader portfolio with a catalog of more than 300,000 products, including many of the most respected brands in the industry, greater geographic reach, and an unmatched combination of industry-leading capabilities.”

PRODUCTS AND SERVICES

http://www.sigmaaldrich.com/configurator/servlet/DesignCenter?btnOpen_0.x=1

http://www.sigmaaldrich.com/content/dam/sigma-aldrich/common/quality-products.jpg

Thermo Fisher Scientific Inc.  MA  NYSE :TMO 

http://thermofisher.com/

 Thermo Fisher Scientific Inc. is a provider of analytical instruments, equipment, reagents and consumables, software and services for research, manufacturing, analysis, discovery and diagnostics. The company operates through four segments: Life Sciences Solutions, provides reagents, instruments and consumables used in biological and medical research, discovery and production of new drugs and vaccines as well as diagnosis of disease; Analytical Instruments, provides instruments, consumables, software and services that are used in the laboratory; Specialty Diagnostics, offers diagnostic test kits, reagents, culture media, instruments and associated products, and Laboratory Products and Services, offers self-manufactured and sourced products for the laboratory.

SOURCE

http://REUTERS.com

PRODUCTS AND SERVICES

Oligos Value – Standard – Plate
Primers
Probes
Nucleotides

BRANDS

THERMO SCIENTIFIC
APPLIED BIOSYSTEMS
INVITROGEN
FISHER SCIENTIFIC
UNITY LAB SERVICES

PARTNERSHIPS

AFFYMETRIX : NASDAQ : AFFX : affymetrix.com/

WALTHAM, Mass. & SANTA CLARA, Calif.–(BUSINESS WIRE)–Jan. 8, 2016– Thermo Fisher Scientific Inc. (NYSE:TMO), the world leader in serving science, and Affymetrix Inc. (NASDAQ:AFFX), a leading provider of cellular and genetic analysis products, today announced that their boards of directors have unanimously approved Thermo Fisher’s acquisition of Affymetrix for $14.00 per share in cash. The transaction represents a purchase price of approximately $1.3 billion.

SOURCE

http://BUSINESSWIRE.com

TriLink Biotechnologies  CA  

http://www.com/

PRODUCTS

Oligonucleotides

DNA Oligos
RNA Oligos
Modified Oligos
Specialty Oligos

Nucleotides

NTPs (Nucleoside Triphosphates)
Biphosphates
Monophosphates

SERVICES

Custom Chemistry
Reagents
Aptamers

PARTNERSHIPS

LIFE TECHNOLOGIES,
TERMO FISHER SCIENTIFIC since July 2015 thermofisher.com/
GENMARK genmarkdx.com/

SOURCE

http://trilinkbiotech.com/

Affymetrix to Stick With Thermo Fisher’s Takeover Proposal

Posted in Computational Biology/Systems and Bioinformatics, Exosomes, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Investment in Technological Breakthrough, Mutagenesis, tagged AgBio, and proteins, Antibodies, clinical markets, cytogenetics, ELISAs, gene expression, GeneChip, genetic analysis, genotyping, life sciences research, microarray technology, multiplex RNA, multiplexed and parallel analysis of biological systems at the cell, protein and genetic level, protein assay, reproductive health, single-cell assays, single-cell biology on January 12, 2016| Leave a Comment »

UPDATED on 3/28/2016

Affymetrix to Stick With Thermo Fisher’s Takeover Proposal

By MICHAEL J. de la MERCED MARCH 28, 2016

SAN FRANCISCO — What briefly appeared to be a potential bidding war for Affymetrix, a genetics analysis technology maker, fizzled out on Monday after the company chose to stick with a takeover bid from Thermo Fisher Scientific over a higher bid from a Chinese-backed suitor.

In a statement, Affymetrix reiterated its support for the $14-a-share offer from Thermo Fisher that it accepted in January.

http://www.nytimes.com/2016/03/29/business/dealbook/affymetrix-to-stick-with-thermo-fishers-takeover-proposal.html?&moduleDetail=section-news-3&action=click&contentCollection=DealBook&region=Footer&module=MoreInSection&version=WhatsNext&contentID=WhatsNext&pgtype=article

UPDATED on 3/23/2016

Affymetrix Postpones Stockholder Meeting as Origin Ups Acquisition Offer; Board Backs Thermo Bid

Mar 23, 2016

In a statement, Affy said that based on the terms of the new offer, it determined that failure to engage with Origin on its bid could reasonably be expected to be “inconsistent with the board’s duties under Delaware law.”

However, Affy said that its board continues to recommend that its stockholders vote in favor of the adoption of the merger agreement with Thermo Fisher, explaining that it “has not determined that the Origin proposal is in fact a ‘superior proposal’ for purposes of the merger agreement with Thermo Fisher and is not making an adverse recommendation change.

“We fully expect that the Affymetrix board of directors will promptly conclude that our transaction remains the only bona fide alternative for Affymetrix stockholders and, as contemplated by the terms of our merger agreement, will definitively recommend against the Origin Technologies proposal and in favor of the Thermo Fisher transaction prior to the upcoming stockholder meeting,” Thermo Fisher President and CEO Marc Casper said in a statement this morning.

“Origin Technologies has still not addressed the fundamental flaws of its proposal, which has remained from its first announcement highly contingent, uncertain, and insufficient,” he added.

SOURCE

a GenomeWeb staff reporter

https://www.genomeweb.com/microarrays-multiplexing/affymetrix-postpones-stockholder-meeting-origin-ups-acquisition-offer-board?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20News:%20Affymetrix%20Postpones%20Stockholder%20Meeting%20as%20Origin%20Ups%20Acquisition%20Offer;%20Board%20Backs%20Thermo%20Bid%20-%2003/23/2016%2010:45:00%20AM

UPDATED on 3/21/2016

Former Affymetrix Execs Offer to Buy Company in Alternative to Thermo Fisher Deal

Mar 18, 2016

a GenomeWeb staff reporter

NEW YORK (GenomeWeb) – Origin Technologies Corporation, founded by former Affymetrix executives for the purpose of purchasing the company, proposed today to acquire Affy for $16.10 per share in an all-cash transaction valued at approximately $1.5 billion.

The proposal comes about a week before Affy shareholders are scheduled to vote on a different deal, Thermo Fisher Scientific’s proposed acquisition of Affy for approximately $1.3 billion, which the boards of directors of both firms unanimously approved in January.

According to a letter sent by Origin to Affymetrix today, its proposal represents a 75 percent premium to Affymetrix’s unaffected closing share price of $9.21 on the last trading day prior to the announcement of Thermo Fisher’s proposed acquisition.

Fully financed by SummitView Capital, Origin said its all-cash offer represents a 15 percent premium for Affy stockholders relative to the proposed transaction with Thermo, under which stockholders would receive $14.00 per share in cash.

As part of the offer, Origin also pledged to fund payment of the $55 million termination fee that would be due to Thermo under the terms of Thermo and Affy’s January agreement.

Wei Zhou, president of the newly formed Origin, wrote in the letter to Affy today that Origin strongly believes that its offer is superior to Thermo’s based on several criteria.

First, it offers substantially higher value to Affy’s stockholders, he said. Additionally, Origin believes it is in a better position to help Affy achieve its potential as a standalone, global company focused on genomics and proteomics. The deal would also offer an opportunity to acquire new technologies in the complete human genome sequencing space, Zhou wrote.

If the Origin-Affy merger goes through, Origin would have a separate option of combining with another company founded by Zhou in 2009, Centrillion Technology Holdings Corporation.

SOURCE

https://www.genomeweb.com/business-news/former-affymetrix-execs-offer-buy-company-alternative-thermo-fisher-deal

Affymetrix: Sales $350 million, Acquisition Price $1.3 billion – Advantages: Cytogenetics, Genotyping and Gene Expression Analysis

Reporter: Aviva Lev-Ari, PhD, RN

Thermo Fisher Scientific Inc.

NYSE: TMO – Jan 12 1:13 PM EST

136.60

1.72 (1.28%)

Thermo Fisher Scientific to acquire Affymetrix for $1.3 billion

WALTHAM, Mass. – Thermo Fisher Scientific Inc., announced Jan. 8 that it has agreed to acquire Affymetrix Inc. for $14.00 per share in cash, or roughly $1.3 billion. The transaction, approved by the boards of directors of both companies is pending shareholder approval and is expected to close in the second quarter this year.

Santa Clara, Calif.-based Affymetrix was founded in 1992 and is a pioneer in the field of

microarray technology, launching its
GeneChip line in 1994. Today, the company serves both the

life sciences research and
clinical markets

Over the past ten years, the company has broadened its portfolio of tools that enable both

multiplexed and
parallel analysis of
biological systems at the cell, protein and genetic level.

Notable acquisitions for Affymetrix have included genetic tools company ParAllele Bioscience (2005), genetic, protein and cellular analysis provider Panomics (2008), and eBioscience (2012), which included one of the world’s largest selections of

antibodies,
ELISAs, and
proteins

for life science research and diagnostics.

“The acquisition of Affymetrix will strengthen our leadership in biosciences and create new market opportunities for us in genetic analysis,” said Marc N. Casper, president and CEO of Thermo Fisher Scientific. “In biosciences, the company’s antibody portfolio will significantly expand our offering in the fast-growing flow cytometry market, and customers will have greater access to these products through our global scale and commercial reach. In genetic analysis, Affymetrix’s technologies are highly complementary and present new opportunities for us in targeted

clinical and
applied markets.”

According to Frank Whitney, president and CEO of Affymetrix, the acquisition will allow the company to continue to build upon the close relationships it has created with customers, while deepening its reach into the biopharma market. “We are excited about the opportunity to combine our portfolios and strengthen our position in high-growth markets such as

single-cell biology
reproductive health and
AgBio

According to information provided by Thermo Fisher, benefits of the acquisition include expanding its offerings of its antibody portfolio via the eBioscience line of products, which also includes

multiplex RNA,
protein assay
single-cell assays
genetic analysis capabilities via complementary products used in

cytogenetics
genotyping and
gene expression.

Thermo expects Affymetrix will add $0.10 in adjusted earnings per share in the first full year of ownership, while creating $70 million in operational savings by year three. Affymetrix has annual revenues of approximately $350 million and will be integrated within Thermo Fisher’s Life Sciences Solutions business unit.

SOURCE

http://www.thejournalofprecisionmedicine.com/thermo-fisher-scientific-to-acquire-affymetrix-for-1-3-billion/

People with blood type O have been reported to be protected from coronary heart disease, cancer, and have lower cholesterol levels.

Posted in Exosomes, Genome Biology, Genomic Testing: Methodology for Diagnosis, Immuno-Oncology & Genomics, Immunodiagnostics, Immunology, Innovation in Immunology Diagnostics, Mutagenesis, Population Health Management, Population Health Management, Genetics & Pharmaceutical on January 11, 2016| Leave a Comment »

People with blood type O have been reported to be protected from coronary heart disease, cancer, and have lower cholesterol levels.

Reporter: Aviva Lev-Ari, PhD, RN

The New England Centenarian Study (NECS) led by Boston University identified 4 key genetic influences in Long-life:

1. ABO Locus

Controls blood type. The study results showed that centenarians are more likely to have the O blood group than controls. People with blood type O have been reported to be protected from coronary heart disease, cancer, and have lower cholesterol levels.

aging_genome_longevity_blood_type_ABO_genes

(Source: Wikipedia Commons)

2. CDKN2B/ANRIL

Implicated in the regulation of the cell life cycle, SNPs from this region have previously been found to be associated with a surprising diversity of age-related diseases. These include cardiovascular disease, type 2 diabetes, intracranial aneurisms, amyotrophic lateral sclerosis (ALS) and several cancers in the case of Anril (through a study at the Paris Descartes University).

For cardiovascular disease, this locus shows the strongest association of any locus in the genome, with each copy of the risk allele increasing one’s risk of disease by 20–30%.

3. APOE/TOMM40

APOE was initially investigated because its ɛ4 allele was known to increase the risk of Alzheimer’sand coronary artery disease, and in the study the disease-allele was shown to be depleted in long-lived populations.

There was also a relationship between the locus and incidence of age-related macular degeneration (vision loss) and total cholesterol levels.

4. SH2B3/ATXN2

Variation in this locus has been associated with a wide variety of diseases, including rheumatoid arthritis, type 2 diabetes, coronary artery disease, blood pressure and cholesterol levels.

iGWAS analysis also showed a protective SNP against lung and pancreatic cancers and promoting good bone mineral density. SH2B3 specifically encodes a signaling protein, and loss-of-function mutations in the invertebrate equivalent gene (Lnk) in fruit flies (Drosophila) was also shown to result in an extended lifespan.

SOURCE

http://labiotech.eu/genomics-holy-grail-secret-behind-aging-longevity-is-genetic/

Read Full Post »

Posted in Big Data, BioIT: BioInformatics, Cell Biology, Chemical Genetics, Clinical Genomics, Curation, Exosomes, Gene Regulation and Evolution, Genome Biology, tagged DNA, Exome sequencing, genome, mutations, Proteins on November 17, 2015| Leave a Comment »

Exosomes

Larry H. Bernstein, MD, FCAP, Curator

LPBI

Human Exomes Galore

A new database includes complete sequences of protein-coding DNA from 60,706 individuals.

By Karen Zusi | November 16, 2015

http://www.the-scientist.com//?articles.view/articleNo/44483/title/Human-Exomes-Galore/

The ability to sequence a person’s entire genome has led many researchers to hunt for the genetic causes of certain diseases. But without a larger set of genomes to compare mutations against, putting these variations into context is difficult. An international group of researchers has banked the full exomes of 60,706 individuals in a database called the Exome Aggregation Consortium (ExAC). The team’s analaysis, posted last month (October 30) on the preprint server bioRxiv, was presented at the Genome Science 2015 conference in Birmingham, U.K. (September 7).

Led by Daniel MacArthur from the Broad Institute of MIT and Harvard, the research team collected exomes from labs around the world for its dataset. “The resulting catalogue of human genetic diversity has unprecedented resolution,” the authors wrote in their preprint. Many of the variants observed in the dataset occurred only once.

“This is one of the most useful resources ever created for medical testing for genetic disorders,” Heidi Rehm, a clinical lab director at Harvard Medical School, told Science News.

Among other things, the team found 3,230 genes that are highly conserved across exomes, indicating likely involvement in critical cellular functions. Of these, 2,557 are not associated with diseases. The authors hypothesized that these genes, if mutated, either lead to embryonic death—before a problem can be diagnosed—or cause rare diseases that have not yet been genetically characterized.

“We should soon be able to say, with high precision: If you have a mutation at this site, it will kill you. And we’ll be able to say that without ever seeing a person with that mutation,” MacArthur said during his Genome Science talk, according to The Atlantic.

This is not the complete set of essential genes in the human body, David Goldstein, a geneticist at Columbia University in New York City, pointed out to Nature. Only by studying more exomes will researchers be able to refine that number, he noted.

Analysis of protein-coding genetic variation in 60,706 humans

, , , , , et al.

http://biorxiv.org/content/early/2015/10/30/030338 doi: http://dx.doi.org/10.1101/030338

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities. The resulting catalogue of human genetic diversity has unprecedented resolution, with an average of one variant every eight bases of coding sequence and the presence of widespread mutational recurrence. The deep catalogue of variation provided by the Exome Aggregation Consortium (ExAC) can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 79% of which have no currently established human disease phenotype. Finally, we show that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human knockout variants in protein-coding genes.

Analysis of protein-coding genetic variation in 60,706 humans https://t.co/z0PtB4c8aY

Over the last five years, the widespread availability of high-throughput DNA sequencing technologies has permitted the sequencing of the whole genomes or exomes (the 18 protein-coding regions of genomes) of over half a million humans. In theory, these data represent a powerful source of information about the global patterns of human genetic variation, but in practice, are difficult to access for practical, logistical, and ethical reasons; in addition, the inconsistent processing complicates variant-calling pipelines used by different groups. Current publicly available datasets of human DNA sequence variation contain only a small fraction of all sequenced samples: the Exome Variant Server, created as part of the NHLBI Exome Sequencing Project (ESP)1, contains frequency information spanning 6,503 exomes; and the 1000 Genomes (1000G) Project, which includes individual-level genotype data from whole-genome and exome sequence data for 2,504 individuals2.

Databases of genetic variation are important for our understanding of human population history and biology1–5, but also provide critical resources for the clinical interpretation of variants observed in patients suffering from rare Mendelian diseases6,7. The filtering of candidate variants by frequency in unselected individuals is a key step in any pipeline for the discovery of causal variants in Mendelian disease patients, and the efficacy of such filtering depends on both the size and the ancestral diversity of the available reference data.

Here, we describe the joint variant calling and analysis of high-quality variant calls across 60,706 human exomes, assembled by the Exome Aggregation Consortium (ExAC; exac.broadinstitute.org). This call set exceeds previously available exome-wide variant databases by nearly an order of magnitude, providing unprecedented resolution for the analysis of very low-frequency genetic variants. We demonstrate the application of this data set to the analysis of patterns of genetic variation including the discovery of widespread mutational recurrence, the inference of gene-level constraint against 10 truncating variation, the clinical interpretation of variation in Mendelian disease genes, and the discovery of human “knockout” variants in protein-coding genes.

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Deleterious variants are expected to have lower allele frequencies than neutral ones, due to negative selection. This theoretical property has been demonstrated previously in human population sequencing data18,19 and here (Figure 1d, Figure 1e). This allows inference of the degree of natural selection against specific functional classes of variation: however, mutational recurrence as described above indicates that allele frequencies observed in ExAC-scale samples are also skewed by mutation rate, with 10 more mutable sites less likely to be singletons (Figure 2c and Extended Data Figure 4d). Mutation rate is in turn non-uniformly distributed across functional classes – for instance, stop lost mutations can never occur at CpG dinucleotides (Extended Data Figure 4e). We corrected for mutation rates (Supplementary Information) by creating a mutability-adjusted proportion singleton (MAPS) metric. This metric reflects (as expected) strong selection against predicted PTVs, as well as missense variants predicted by conservation-based methods to be deleterious (Figure 2e).

The deep ascertainment of rare variation in ExAC also allows us to infer the extent of 19 selection against variant categories on a per-gene basis by examining the proportion of 20 variation that is missing compared to expectations under random mutation. Conceptually similar approaches have been applied to smaller exome datasets13,20 but have been underpowered, particularly for the analysis of depletion of PTVs. We compared the observed number of rare (MAF <0.1%) variants per gene to an expected number derived from a selection neutral, sequence-context based mutational model13. The model performs extremely well in predicting the number of synonymous variants, which should be under minimal purifying selection, per gene (r = 0.98; Extended Data Figure 5).

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Critically, we note that LoF-intolerant genes include virtually all known severe haploinsufficient human disease genes (Figure 3b), but that 79% of LoF-intolerant genes have not yet been assigned a human disease phenotype despite the clear evidence for extreme selective constraint (Supplementary Information 4.11). These likely represent either undiscovered severe dominant disease genes, or genes in which loss of a single copy results in embryonic lethality.

The most highly constrained missense (top 25% missense Z scores) and PTV (pLI ≥0.9) genes show higher expression levels and broader tissue expression than the least constrained genes24 (Figure 3c). These most highly constrained genes are also depleted for eQTLs (p < 10-9 for missense and PTV; Figure 3d), yet are enriched within genome-wide significant trait-associated loci (χ2 p < 10-14, Figure 3e). Intuitively, genes intolerant of PTV variation are dosage sensitive: natural selection does not tolerate a 50% deficit in expression due to the loss of single allele. It is therefore unsurprising that these genes are also depleted of common genetic variants that have a large enough effect on expression to be detected as eQTLs with current limited sample sizes. However, smaller changes in the expression of these genes, through weaker eQTLs or functional variants, are more likely to contribute to medically relevant phenotypes. Therefore, highly constrained genes are dosage-sensitive, expressed more broadly across tissues (as expected for core cellular processes), and are enriched for medically relevant variation.

Finally, we investigated how these constraint metrics would stratify mutational classes according to their frequency spectrum, corrected for mutability as in the previous section (Figure 3f). The effect was most dramatic when considering stop-gained variants in the LoF-intolerant set of genes. For missense variants, the missense Z score offers information additional to Polyphen2 and CADD classifications, indicating that gene-level measures of constraint offer additional information to variant-level metrics in assessing potential pathogenicity.

We assessed the value of ExAC as a reference dataset for clinical sequencing approaches, which typically prioritize or filter potentially deleterious variants based on functional consequence and allele frequency6. To simulate a Mendelian variant analysis, we filtered variants in 100 ExAC exomes per continental population against ESP (the previous default reference data set for clinical analysis) or the remainder of ExAC, removing variants present at ≥0.1% allele frequency, a filter recommended for dominant 16 disease variant discovery6. Filtering on ExAC reduced the number of candidate protein-altering variants by 7-fold compared to ESP, and was most powerful when the highest 18 allele frequency in any one population (“popmax”) was used rather than average (“global”) allele frequency (Figure 4a). ESP is not well-powered to filter at 0.1% AF without removing many genuinely rare variants, as AF estimates based on low allele counts are both upward-biased and imprecise (Figure 4b). We thus expect that ExAC will provide a very substantial boost in the power and accuracy of variant filtering in Mendelian disease projects.

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The above curation efforts confirm the importance of allele frequency filtering in analysis of candidate disease variants. However, literature and database errors are prevalent even at lower allele frequencies: the average ExAC exome contains 0.89 reportedly Mendelian variants in well-characterized dominant disease genes at <1% popmax AF and 0.20 at <0.1% popmax AF. This inflation likely results from a combination of false reports of pathogenicity and incomplete penetrance, as we show for PRNP in the accompanying work [Minikel et al, submitted]. The abundance of rare functional variation in many disease genes in ExAC is a reminder that such variants should not be assumed to be causal or highly penetrant without careful segregation or case-control analysis28,7.

We investigated the distribution of PTVs, variants predicted to disrupt protein-coding genes through the introduction of a stop codon or frameshift or the disruption of an essential splice site; such variants are expected to be enriched for complete loss-of-function of the impacted genes. Naturally-occurring PTVs in humans provide a model for the functional impact of gene inactivation, and have been used to identify many genes in 6 which LoF causes severe disease31, as well as rare cases where LoF is protective against disease32.

Among the 7,404,909 HQ variants in ExAC, we found 179,774 high-confidence PTVs (as 10 defined in Supplementary Information Section 6), 121,309 of which are singletons. This 11 corresponds to an average of 85 heterozygous and 35 homozygous PTVs per individual (Figure 5a). The diverse nature of the cohort enables the discovery of substantial numbers of novel PTVs: out of 58,435 PTVs with an allele count greater than one, 33,625 occur in only one population. However, while PTVs as a category are extremely rare, the majority of the PTVs found in any one person are common, and each individual 16 has only ~2 singleton PTVs, of which 0.14 are found in PTV-constrained genes (pLI 17 >0.9). The site frequency spectrum of these variants across the populations represented in ExAC recapitulates known aspects of demographic models, including an increase in intermediate-frequency (1%-5%) PTVs in Finland33 and relatively common (>0.1%) PTVs in Africans (Figure 5b).

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Discussion Here we describe the generation and analysis of the most comprehensive catalogue of 29 human protein-coding genetic variation to date, incorporating high-quality exome sequencing data from 60,706 individuals of diverse geographic ancestry. The resulting call set provides unprecedented resolution for the analysis of very low-frequency protein-coding variants in human populations, as well as a powerful resource for the clinical interpretation of genetic variants observed in disease patients. The complete frequency CC-BY-ND 4.0 International license for this preprint is the author/funder. It is made available under a bioRxiv preprint first posted online October 30, 2015;
http://dx.doi.org/10.1101/030338 ; The copyright holder and annotation data from this call-set has been made freely available through a public website [exac.broadinstitute.org]

The ExAC resource provides the largest database to date for the estimation of allele frequency for protein-coding genetic variants, providing a powerful filter for analysis of candidate pathogenic variants in severe Mendelian diseases. Frequency data from ESP1 have been widely used for this purpose, but those data are limited by population diversity and by resolution at allele frequencies ≤0.1%. ExAC therefore provides 21 substantially improved power for Mendelian analyses, although it is still limited in power at lower allele frequencies, emphasizing the need for more sophisticated pathogenic variant filtering strategies alongside on-going data aggregation efforts. ExAC also highlights an unexpected tolerance of many disease genes to functional variation, and reveals that the literature and public databases contain an inflated number of reportedly pathogenic variants across the frequency spectrum, indicating a need for stringent criteria for assertions of pathogenicity.

Finally, we show that different populations confer different advantages in the discovery of gene-disrupting PTVs, providing guidance for projects seeking to identify human “knockouts” to understand gene function. Individuals of African ancestry have more PTVs (140 on average), with this enrichment most pronounced at allele frequencies above 1% (Figure 5b). Finnish individuals, as a result of a population bottleneck, are depleted at the lowest (<0.1%) allele frequencies but have a peak in frequency at 1-5% (Figure 5b). However, these differences are diminished when considering only LoF-constrained (pLI > 0.9) genes (Extended Data Figure 10). Sampling multiple populations would likely be a fruitful strategy for a researcher investigating common PTV variation. However, discovery of homozygous PTVs is markedly enhanced in the South Asia samples, which come primarily from a Pakistani cohort with 38.3% of individuals self- reporting as having closely related parents, emphasizing the extreme value of consanguineous cohorts for “human knockout” discovery (Figure 5d) [Saleheen et al., to 8 be co-submitted].

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While the ExAC dataset dramatically exceeds the scale of previously available frequency reference datasets, much remains to be gained by further increases in sample size. Indeed, the fact that even the rarest transversions have mutational rates13 on the order of 1 x 10-9 implies that almost all possible non-lethal SNVs likely exist in some person on Earth. ExAC already includes >70% of all possible protein-coding CpG transitions at well-covered sites; order of magnitude increases in sample size will eventually lead to saturation of other classes of variation.

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Technology: With a unique program, the US government has managed to drive the cost of genome sequencing down to $1,000

Posted in BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Exosomes, Genomic Testing: Methodology for Diagnosis on March 25, 2014| Leave a Comment »

Technology: With a unique program, the US government has managed to drive the cost of genome sequencing down to $1,000

Reporter: Aviva Lev-Ari, PhD, RN

See on Scoop.it – Cardiovascular and vascular imaging

With a unique program, the US government has managed to drive the cost of genome sequencing down towards a much-anticipated target.

The quest to sequence the first human genome was a massive undertaking. Between 1990 and the publication of a working draft in 2001, more than 200 scientists joined forces in a $3-billion effort to read the roughly 3 billion bases of DNA that comprise our genetic material (International Human Genome Sequencing Consortium Nature 409, 860–921; 2001).

It was a grand but sobering success. The project’s advocates had said that it would reveal ‘life’s instruction book’, but in fact it did not make it possible to interpret how the instructions encoded in DNA were transformed into biology. Understanding how DNA actually influences health and disease would require studying examples of the links between genes and biology in thousands, perhaps millions, more people. The dominant technology at the time was Sanger sequencing, an inherently slow, labour-intensive process that works by making copies of the DNA to be sequenced that include chemically modified and fluorescently tagged versions of the molecule’s building blocks. One company, Applied Biosystems in Foster City, California, provided the vast majority of the sequencers to a limited number of customers — generally, large government-funded laboratories — and there was little incentive for it to reinvent its core technology.

A $7-million award from the NHGRI allowed the company to commercialize a technology called pyrosequencing, which was the first to begin chipping away at Applied Biosystems’ monopoly. The funding commitments also ultimately helped to convince private investors to enter the market. Stephen Turner, founder and chief technology officer of Pacific Biosciences in Menlo Park, California, says that his company’s 2005 NHGRI grant of $6.6 million helped to attract subsequent venture-capital funding.

The government program has invested $88 million in technologies based on nanopores and nanogaps. The form of this technology closest to the market involves reading bases as they are threaded through a pore (see Nature 456, 23–25; 2008), a method that has long promised to save costs and time by reading DNA while it is processed. It would negate the need for expensive and slow reactions to make lots of copies of the molecule. But solving basic issues, including how to move the DNA through the pore slowly enough, has been a major challenge. The NHGRI has funded work to overcome these hurdles — including $9.3 million given to collaborators of the company now ushering the concept to market, UK-based Oxford Nanopore Technologies (Nature http://doi.org/rvm; 2014).

Sequencing still needs much improvement, especially in terms of quality. For all of Sanger sequencing’s high cost, it remains the benchmark for accuracy. And sequencing costs are no longer dropping as quickly as they were a few years ago.

But researchers are optimistic that another technology will emerge to challenge Illumina. Most think, in fact, that the crucial questions for the field will shift away from technology. Now that sequencing is cheap enough to talk about scanning every patient’s genome, or at least the protein-coding portion of it, it is still not clear how that information will translate into improved care (Nature http://doi.org/rvq; 2014). These more complex issues will require another great leap in genomic science — one that could make the trouncing of Moore’s law seem easy

See on www.nature.com

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