Taking the gamble out of DNA sequencing: How much can be learned in a large-scale experiment

Feb. 24, 2013 ? Two USC scientists have developed an algorithm that could help make DNA sequencing affordable enough for clinics -- and could be useful to researchers of all stripes.

Andrew Smith, a computational biologist at the USC Dornsife College of Letters, Arts and Sciences, developed the algorithm along with USC graduate student Timothy Daley to help predict the value of sequencing more DNA, to be published in Nature Methods on February 24.

Extracting information from the DNA means deciding how much to sequence: sequencing too little and you may not get the answers you are looking for, but sequence too much and you will waste both time and money. That expensive gamble is a big part of what keeps DNA sequencing out of the hands of clinicians. But not for long, according to Smith.

"It seems likely that some clinical applications of DNA sequencing will become routine in the next five to 10 years," Smith said. "For example, diagnostic sequencing to understand the properties of a tumor will be much more effective if the right mathematical methods are in place."

The beauty of Smith and Daley's algorithm, which predicts the size and composition of an unseen population based on a small sample, lies in its broad applicability.

"This is one of those great instances where a specific challenge in our research led us to uncover a powerful algorithm that has surprisingly broad applications," Smith said.

Think of it: how often do scientists need to predict what they haven't seen based on what they have? Public health officials could use the algorithm to estimate the population of HIV positive individuals; astronomers could use it to determine how many exoplanets exist in our galaxy based on the ones they have already discovered; and biologists could use it to estimate the diversity of antibodies in an individual.

The mathematical underpinnings of the algorithm rely on a model of sampling from ecology known as capture-recapture. In this model, individuals are captured and tagged so that a recapture of the same individual will be known -- and the number of times each individual was captured can be used to make inferences about the population as a whole.

In this way scientists can estimate, for example, the number of gorillas remaining in the wild. In DNA sequencing, the individuals are the various different genomic molecules in a sample. However, the mathematical models used for counting gorillas don't work on the scale of DNA sequencing.

"The basic model has been known for decades, but the way it has been used makes it highly unstable in most applications. We took a different approach that depends on lots of computing power and seems to work best in large-scale applications like modern DNA sequencing," Daley said.

Scientists faced a similar problem in the early days of the human genome sequencing project. A mathematical solution was provided by Michael Waterman of USC, in 1988, which found widespread use. Recent advances in sequencing technology, however, require thinking differently about the mathematical properties of DNA sequencing data.

"Huge data sets required a novel approach. I'm very please it was developed here at USC," said Waterman.

This research was funded by grants from the National Institutes of Health National Human Genome Research Institute (R01 HG005238 and P50 HG002790).

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Story Source:

The above story is reprinted from materials provided by University of Southern California, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Timothy Daley, Andrew D Smith. Predicting the molecular complexity of sequencing libraries. Nature Methods, 2013; DOI: 10.1038/nmeth.2375

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/3-uOSnhnewE/130224142825.htm

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Zero Hour at the Vatican: A Bitter Struggle for Control of the Catholic Church

What areas do you think the Church needs reform in?

__________________
?When men open their lips against [the truth] they do not injure me, but injure themselves. ? When things that are of the greatest importance are passed over by weak-minded men without even a thought, I want to see truth in all its bearings and hug it to my bosom. I believe all that God ever revealed, and I never hear of a man being damned for believing too much; but they are damned for unbelief.? - Joseph Smith Jr.

?Study the Bible, and as many of our books as you can get; pray to the Father in the name of Jesus Christ, have faith in the promises made to the fathers, and your mind will be guided to the truth.? - Joseph Smith Jr.

Imagine what good we can do if we all joined together, united as followers of Christ - M. Russell Ballard

Source: http://www.usmessageboard.com/religion-and-ethics/279557-zero-hour-at-the-vatican-a-bitter-struggle-for-control-of-the-catholic-church.html

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S&P expects US lawsuit over its mortgage ratings

WASHINGTON (AP) ? The U.S. government is expected to file civil charges against Standard & Poor's Ratings Services, alleging that it improperly gave high ratings to mortgage debt that later plunged in value and helped fuel the 2008 financial crisis.

The charges would mark the first enforcement action the government has taken against a major rating agency involving the worst financial crisis since the Great Depression.

S&P said Monday that the Justice Department had informed the rating agency that it intends to file a civil lawsuit focusing on S&P's ratings of mortgage debt in 2007.

The action does not involve any criminal allegations. Critics have long complained about the government's failure to bring criminal charges against any major Wall Street players involved in the financial crisis. Criminal charges would require a higher burden of proof and carry the threat of jail time.

If S&P is eventually found guilty of civil violations, it could face fines and limits on how it does business.

S&P denies any wrongdoing and says any lawsuit would be without merit.

A federal lawsuit would "disregard" the fact that S&P reviewed the same data on risky mortgages as U.S. government officials, who said publicly in 2007 that the problems in the subprime mortgage market appeared to be limited, the company said in a statement.

In the statement, S&P said it "deeply regrets" that its ratings on some securities "failed to fully anticipate the rapidly deteriorating conditions in the U.S. mortgage market during that tumultuous time."

Justice Department spokeswoman Nanda Chitre declined to comment on the matter.

Judges have previously thrown out claims brought by investors against the rating agencies, on the grounds that their ratings amount to free speech protected by the First Amendment.

But that argument hasn't always succeeded in cases involving investments like those in the expected S&P suit, according to research by The Brattle Group, a consulting firm. That's because those ratings weren't published widely, as most bond ratings are. As a result, several courts have ruled that those ratings do not enjoy free-speech protection.

S&P is a unit of New York-based McGraw-Hill Cos. McGraw-Hill's stock plunged nearly 14 percent Monday after reports surfaced about the government's expected lawsuit.

Moody's Corp., the parent of Moody's Investors Service, another rating agency, closed down nearly 11 percent. The two companies' stocks suffered the biggest percentage drops in the S&P 500 index, which finished down slightly more than 1 percent.

According to a report in the New York Times, the lawsuit will likely be brought this week after settlement talks between the Justice Department and S&P broke down last week. The talks collapsed over federal authorities' insistence that a settlement involve at least $1 billion, the Times reported.

S&P, Moody's, and Fitch Ratings, the third major rating agency, have been blamed for helping fuel the financial crisis by assigning AAA ratings to trillions of dollars in risky securities backed by subprime mortgages. The securities collapsed once the housing bubble burst and home-loan delinquencies soared. Major U.S. banks absorbed tens of billions in losses.

The rating agencies are important arbiters of the creditworthiness of securities traded around the world. The grades they assign can affect a company's ability to raise or borrow money and how much investors will pay for securities it issues.

The securities in the anticipated federal lawsuit are collateralized debt offerings. CDOs are investment vehicles that contain many underlying mortgage loans.

A CDO generally gains in value if borrowers repay. But a wave of defaults can cause them to tumble in value. Soured CDOs contributed to, and intensified, the financial crisis.

Critics have long argued that rating agencies have an inherent conflict of interest: They're paid by the same companies whose products and credit they rate. The agencies have been accused of issuing unduly high ratings before the crisis, in part because of pressure from banks they desired as clients.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/f70471f764144b2fab526d39972d37b3/Article_2013-02-04-Standard%20and%20Poor's-Lawsuit/id-56663336a9614a119815a2d686c915e2

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