Here is a new paper comparing several approaches in non-invasive prenatal diagnostics (NIPD) published in CCLM in June and is available for free at:
It was submitted almost a year ago, but the data is still current.
Rapidly developing next-generation sequencing (NGS) technologies produce a large amount of data across the whole human genome and allow a large number of DNA samples to be analyzed simultaneously. Screening cell-free fetal DNA (cffDNA) obtained from maternal blood using NGS technologies has provided new opportunities for non-invasive prenatal diagnosis (NIPD) of fetal aneuploidies. One of the major challenges to the analysis of fetal abnormalities is the development of accurate and reliable algorithms capable of analyzing large numbers of short sequence reads. Several such algorithms have recently been developed. Here, we provide a review of recent NGS-based NIPD methods as well as the available algorithms for short-read sequence analysis. We furthermore introduce the practical application of these algorithms for the detection of different types of fetal aneuploidies, and compare the performance, cost and complexity of each approach for clinical deployment. Our review identifies several main technologies and trends in NGS-based NIPD. The main considerations for clinical development for NIPD and screening tests using DNA sequencing are: accuracy, intellectual property, cost and the ability to screen for a wide range of chromosomal abnormalities and genetic defects. The cost of the diagnostic test depends on the sequencing method, diagnostic algorithm and volume of the tests. If the cost of sequencing equipment and reagents remains at or around current levels, targeted approaches for sequencing-based aneuploidy testing and SNP-based methods are preferred.
Since the discovery of the cell-free fetal nucleic acid sequences in maternal peripheral blood, several methods for highly accurate and highly sensitive aneuploidy testing using NGS technology either for full genome sequencing or sequencing of targeted areas of the genome were developed. Prenatal tests utilizing these methods are already offered as screening tests for trisomy 21, 18 and 13, reducing the need for risky invasive procedures. Additional clinical trials are underway to validate these methods for use as diagnostic tests for both high-risk pregnancies and screening of the general population. The final decision on the implementation of a NGS-based test for NIPD of aneuploidy in clinical practice should be based on the criteria of high diagnostic accuracy, clinical and cost-effectiveness and the ability to make a diagnosis even in cases where the content of cffDNA is low. Furthermore, large-scale validation studies should be carried out independent from the tests’ manufacturing companies. Tests implemented in a clinical setting should not be time consuming, which is very important in prenatal diagnosis. It is also important to take into account the nationality of the patients in order to implement the test in clinics around the world. Tests should also require a minimal cost of equipment and infrastructure in order to be available to small laboratories around the world. Today NGS-based tests for diagnosis of trisomies 21, 18 and 13 may be combined with ultrasonographic detection and serum markers for more accurate diagnosis of fetal aneuploidy, in order to avoid invasive procedures. Methods utilizing full genome sequencing allow for accurate detection of other autosomal and sex aneuploidies, but are limited by the high cost of sequencing. Sequencing of targeted areas of the genome allows one to significantly lower the cost of sequencing while providing high accuracy and sensitivity in diagnosing common aneuploidies. Methods utilizing parental genotypes, where DNA from one or both parents is available, in addition to common trisomy detection, provide for highly accurate counts of autosomes and sex chromosomes and can be performed using significantly cheaper and easier to operate sequencing equipment. Our review demonstrated that NGS-based NIPD is a rapidly evolving field with many research teams developing and commercializing tests using new technologies and performing large scale clinical trials. As the new NGS technologies become available, new methods for NIPD will be developed that allow the analysis of a broader spectrum of chromosomal abnormalities and genetic diseases, and cost will be reduced. Several commercial NIPD providers developed proprietary fetal quantifiers and protocols for increasing diagnostic accuracy of the tests and these may not be publicly available. All of the reviewed methods bear equipment, technology, cost, intellectual property and performance risk; thus, careful consideration should be given to each of these aspects when deploying or developing NGS-based NIPD in a clinical setting.
Sequencing requirements (see table 2 in the paper for Verinata, Ariosa and Sequenom):
Monday, June 24, 2013
Here is a new paper comparing several approaches in non-invasive prenatal diagnostics (NIPD) published in CCLM in June and is available for free at:
Monday, March 14, 2011
One interesting resource for biomedical research - Aging Research Portfolio shows how much is being spent on various research projects worldwide. Today we tried searching for "Amniocentesis" using its advanced search feature and found that over 90 million dollars were spent by various organizations on that invasive procedure. What would be interesting to see is how much is spent on the Non-invasive prenatal diagnostics.
One interesting project is was "Chorionic villus sampling vs amniocentesis-data center" here is a screenshot:
The National Institute of Child Health and Human Development spent millions of dollars on this project over time...
Aging Limit ID
|5U01DK061230-07||Statistics center for pediatric type 2 diabetes therapy||HIRST KATHRYN||GEORGE WASHINGTON UNIVERSITY||NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES||2008||$28,375,332||0|
|5U01HD019897-11||Nichd networks: data coordinating center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1995||$2,980,055||0|
|5U01HD019897-13||Nichd networks: data coordinating center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1997||$2,839,085||0|
|5U01HD019897-12||Nichd networks: data coordinating center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1996||$2,665,090||0|
|2U01HD019897-09||Data coordinating center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1993||$2,581,536||0|
|5U01HD019897-10||Nichd networks: data coordinating center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1994||$2,480,469||0|
|5U01HD019897-08||Chorionic villus sampling vs amniocentesis-data center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1992||$2,342,231||0|
|5R01HD038940-02||Feasibility of prenatal screening for slo syndrome||HADDOW JAMESE||FOUNDATION FOR BLOOD RESEARCH||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2002||$1,804,263||0|
|1RC2HD064525-01||Cnv atlas of human development||LEDBETTER H,|
|EMORY UNIVERSITY||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2009||$1,727,519||0|
|1R01HD038940-01A1||Feasibility of prenatal screening for slo syndrome||HADDOW JAMESE||FOUNDATION FOR BLOOD RESEARCH||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2001||$1,700,530||0|
|1R01HD031991-01A1||Randomized trial of 11-14 week amniocentesis and ta cvs||JACKSON LAIRDG||THOMAS JEFFERSON UNIVERSITY||National Institute of Child Health and Human Development||1996||$1,506,031||4|
|N01HD043204-008||Prenatal diagnosis trials--fetal cells/maternal blood||BIANCHI DIANAW||TUFTS MEDICAL CENTER||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2000||$1,346,158||0|
|N01HD043204-009||Prenatal diagnosis trials--fetal cells/maternal blood||BIANCHI DIANAW||TUFTS MEDICAL CENTER||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2000||$1,342,310||0|
|5R01HD031991-02||Randomized trial of 11-14 week amniocentesis and ta cvs||JACKSON LAIRDG||THOMAS JEFFERSON UNIVERSITY||National Institute of Child Health and Human Development||1997||$1,312,557||4|
|1R01EB008009-01||Insulin producing cells from amniotic stem cells for diabetes therapy||ATALA ANTHONY||WAKE FOREST UNIVERSITY HEALTH SCIENCES||NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING||2007||$1,058,000||4|
|5R01EB008009-02||Insulin producing cells from amniotic stem cells for diabetes therapy||ATALA ANTHONY||WAKE FOREST UNIVERSITY HEALTH SCIENCES||NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING||2008||$1,025,080||4|
|5R01EB008009-03||Insulin producing cells from amniotic stem cells for diabetes therapy||ATALA ANTHONY||WAKE FOREST UNIVERSITY HEALTH SCIENCES||NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING||2009||$1,025,080||4|
|N01HD043201-010||Prenatal diagnosis trials--fetal cells/maternal blood||JACKSON LAIRDG||THOMAS JEFFERSON UNIVERSITY||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2000||$1,003,876||0|
|N01HD043201-011||Prenatal diagnosis trials--fetal cells/maternal blood||JACKSON LAIRDG||THOMAS JEFFERSON UNIVERSITY||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2000||$981,804||0|
|N01HD043202-009||Prenatal diagnosis trials--fetal cells/maternal blood||EVANS MARKI||WAYNE STATE UNIVERSITY||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2000||$970,355||0|
|5R01HD038940-03||Feasibility of prenatal screening for slo syndrome||KNIGHT GEORGEJ||FOUNDATION FOR BLOOD RESEARCH||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2003||$887,976||0|
|5R01HD031991-03||Randomized trial of 11-14 week amniocentesis and ta cvs||JACKSON LAIRDG||THOMAS JEFFERSON UNIVERSITY||National Institute of Child Health and Human Development||1998||$876,479||4|
|N01HD043203-009||Prenatal diagnosis trials--fetal cells/maternal blood||SHULMAN LEEP||UNIVERSITY OF TENNESSEE HEALTH SCI CTR||EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT||2000||$600,000||0|
|3U01HD019897-08S1||Chorionic villus sampling vs amniocentesis-data center||BAIN RAYMONDP||GEORGE WASHINGTON UNIVERSITY||National Institute of Child Health and Human Development||1993||$578,690||4|
|5U10HD027861-07||Multicenter network of maternal-fetal medicine units||MOAWAD ATEFH||UNIVERSITY OF CHICAGO||National Institute of Child Health and Human Development||1997||$537,939||0|
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Thursday, February 10, 2011
Sequenom's Non-invasive Down Syndrome test shows 100% sensitivity and 99.7% specificity in a major clinical trial
Those now if you are in your 40s and get pregnant sometime closer to the end of the year, most likely you won't need to go for the amniocentesis. Sequenom just confirmed that their non-invasive T21 test is just as accurate as the amnio, but without side effects!
Unfortunately, the company's marketing and PR department is the complete opposite of their R&D. The only mention of the test accuracy data is in their brief press release below off PR Newswire. We did not pick it up from WSJ, Bloomberg or Forbes journalists. Their CEO or CMO is not on the air or on TV. And it seems like we are the only blog covering this historic event!
SAN DIEGO, Feb. 10, 2011 /PRNewswire/ -- Sequenom (Nasdaq:SQNM - News) is very pleased to announce publication in the American Journal of Obstetrics and Gynecology (doi: 10.1016/j.ajog.2010.12.060) of Sequenom CMM's "locked assay" study.
The paper entitled "Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting" is available through the 'Articles Online First' section of the American Journal of Obstetrics and Gynecology website – http://www.ajog.org. The article is scheduled to appear in the March issue of the journal to be published both online and in print.
The performance of a massively parallel shotgun sequencing based assay for noninvasive detection of fetal aneuploidy was evaluated on a set of 480 plasma samples from pregnant women at high-risk for fetal chromosomal aneuploidy. Utilizing 449 samples, all 39 trisomy 21 (T21) samples were correctly identified, while one of the 410 euploid samples was misclassified as T21. The overall classification showed 100% sensitivity (95% CI: 89% to 100%) and 99.7 specificity (95% CI: 98.5% to 99%). A total of 31 samples were removed due to insufficient quantity, breakage or failing pre-specified quality control criteria.
"This important study demonstrated that massively parallel shotgun sequencing is a potentially viable path for noninvasive prenatal diagnosis of fetal Trisomy 21 and warrants its validation in a larger clinical validation study," said Harry F. Hixson, Jr. PhD, chairman and chief executive officer of Sequenom. "We are very pleased with the results from the 'locked assay' study and are looking forward to the completion of the larger clinical validation study later this year."
Sequenom Center for Molecular Medicine (Sequenom CMM) initiated its pivotal clinical validation study in late December 2010. This validation study is designed to evaluate the clinical performance of the SensiGene T21 Laboratory Developed Test (LDT) for the detection of an overabundance of chromosome 21 in maternal blood, which is associated with fetal chromosome 21 aneuploidy. Testing of the clinical specimens is being performed at the Sequenom CMM CLIA-certified facility in San Diego.
About Sequenom Center for Molecular Medicine
Sequenom Center for Molecular Medicine (Sequenom CMM®) is a CAP accredited and CLIA-certified specialty reference laboratory dedicated to the development and commercialization of laboratory-developed genetic testing services for prenatal and eye conditions. Utilizing innovative proprietary technologies, Sequenom CMM provides test results that can be used as tools by clinicians in managing patient care. Testing services are available only upon request to physicians. Sequenom CMM works closely with key opinion leaders and experts in obstetrics, retinal care and genetics. The scientists use a variety of sophisticated and cutting-edge methodologies in the development and validation of tests. Sequenom CMM is changing the landscape in genetic diagnostics. Visit http://www.scmmlab.com for more information on laboratory services.
Friday, January 28, 2011
Dennis Lo's paper on non-invasive Down's syndrome diagnostics is finally published in the British Medical Journal
The proof of concept of the test, which will be brought to market to market by the San Diego-based company Sequenom, Inc (NASDAQ: SQNM) sometime this year showed very high accuracy in a reasonably large clinical trial. We salute Dennis Lo and Sequenom on these results and hope that the tests will be launched to general public as soon as possible.
Now that we know that the test works, Sequenom has a moral duty to the pregnant women to bring it to market as soon as possible and reduce the number of unnecessary invasive procedures and resulting spontaneous abortions and damage to the fetus.
Here is a link to the story and Sequenom's press release
Press Release Source: Sequenom, Inc. On Wednesday January 12, 2011, 2:45 pm EST
SAN DIEGO, Jan. 12, 2011 /PRNewswire/ -- Sequenom (Nasdaq:SQNM - News) is very pleased to note the publication in the British Medical Journal (BMJ 2011;342:c7401) of a groundbreaking international study led by our longstanding collaborator, Professor Dennis Lo of The Chinese University of Hong Kong. Building on early work from the Lo laboratory, the present paper is the first report of a large-scale clinical study that validates a noninvasive, plasma DNA-based approach for prenatally detecting Down's syndrome (T21). Sequenom congratulates the research team for their achievements.
Sequenom, Inc. (NASDAQ:SQNM - News) is a life sciences company committed to improving healthcare through revolutionary genetic analysis solutions. Sequenom develops innovative technology, products and diagnostic tests that target and serve discovery and clinical research, and molecular diagnostics markets. The company was founded in 1994 and is headquartered in San Diego, California. Sequenom maintains a Web site at http://www.sequenom.com to which Sequenom regularly posts copies of its press releases as well as additional information about Sequenom. Interested persons can subscribe on the Sequenom Web site to email alerts or RSS feeds that are sent automatically when Sequenom issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the Web site.
31st Annual Meeting
The Pregnancy MeetingTM
Date: February 7, 2011 - February 12, 2011
Location: Hilton San Francisco Union Square
333 O'Farrell St.
San Francisco, CA
Use Group Code: SFM to get the special SMFM rate. Use the link below for online reservations.
Description: The SMFM 31st Annual Meeting will present cutting-edge basic, clinical, and epidemiological research. In addition to oral and poster presentations, attendees will hear from world-renowned leaders in the specialty of maternal-fetal medicine.
Attachments: 2011 Exhibitor Prospectus
EXHIBIT SPACE for the SMFM 2011 ANNUAL MEETING is SOLD OUT.
31st Annual Meeting Preliminary Program
Click on the link above to download a PDF of the meeting brochure.
2011 Poster Instructions
Please click on the link above to download a PDF of the 2011 SMFM poster presentation instructions.
2011 Scientific Forum Agendas
Click on the link above to download a PDF file of the 2011 Scientific Forum Agendas.
AJOG SMFM Manuscript Submission Instructions
Please click on the link above to down load a PDF of the AJOG SMFM Manuscript Submission Guidelines.
Exhibit Floor Plan
Please click on the link above to download the 2011 exhibit floor plan. For more information on 2011 Exhibits, please click here.
On-site Registration form
Please click on the link above to download the on-site meeting registration form.
An article published at Science Daily reveals shocking news:
99% of Pregnant Women in US Test Positive for Multiple Chemicals Including Banned Ones, Study Suggests
nalyzing data for 163 chemicals, researchers detected polychlorinated biphenyls (PCBs), organochlorine pesticides, perfluorinated compounds (PFCs), phenols, polybrominated diphenyl ethers (PBDEs), phthalates, polycyclic aromatic hydrocarbons (PAHs) and perchlorate in 99 to 100 percent of pregnant women. Among the chemicals found in the study group were PBDEs, compounds used as flame retardants now banned in many states including California, and dichlorodiphenyltrichloroethane ( DDT), an organochlorine pesticide banned in the United States in 1972.
Bisphenol A (BPA), which makes plastic hard and clear, and is found in epoxy resins that are used to line the inside of metal food and beverage cans, was identified in 96 percent of the women surveyed. Prenatal exposure to BPA has been linked to adverse health outcomes, affecting brain development and increasing susceptibility to cancer later in life, according to the researchers.
Findings will be published in Environmental Health Perspectives on Jan. 14.
Tuesday, November 30, 2010
One interesting article at Science Daily today. It is not directly related to prenatal diagnostics, but will be interesting to anyone in the field.
Researchers have found that the naturally-occurring hormone and neurotransmitter oxytocin intensifies men's memories of their mother's affections during childhood. The study was published November 29 in Proceedings of the National Academy of Sciences.
Researchers at the Seaver Autism Center for Research and Treatment at Mount Sinai School of Medicine wanted to determine whether oxytocin, a hormone and neurotransmitter that is known to regulate attachment and social memory in animals, is also involved in human attachment memories. They conducted a randomized, double-blind, placebo-controlled, cross-over trial, giving 31 healthy adult men oxytocin or a placebo delivered nasally on two occasions. Prior to administering the drug/placebo, the researchers measured the men's attachment style. About 90 minutes after administering the oxytocin or the placebo the researchers assessed participants' recollection of their mother's care and closeness in childhood.