NGS分析嘴仗：RNA studies under fire# Biology - 生物学
g*n
1 楼
某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
自己宿舍门
口：今日青春女生，明日成功女性。
自己宿舍门
口：今日青春女生，明日成功女性。
o*r
2 楼
今天的nature news:
http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
RNA studies under fire
High-profile results challenged over statistical analysis of sequence data.
Erika Check Hayden
25 April 2012
Article tools
Print
Email
Download PDF
Rights and Permissions
Share/bookmark
High-throughput RNA sequencing has yielded some unexpected results in the
past few years — including some that seem to rewrite conventional wisdom in
genetics. But a few of those findings are now being challenged, as
computational biologists warn of the statistical pitfalls that can lurk in
data-intensive studies.
The latest case centres on imprinted genes. Humans and most other animals
inherit two copies of most genes, one from each parent. But in some cases,
only one copy is expressed; the other copy is silenced. In such cases, the
gene is described as being imprinted. In July 2010, a team led by Catherine
Dulac and Christopher Gregg, both then at Harvard University in Cambridge,
Massachusetts, published a study1 in Science estimating that 1,300 mouse
genes — an order of magnitude more than previously known — were imprinted.
Now, researchers are arguing that a flawed analysis led Dulac and Gregg to
vastly overestimate imprinting in their paper. “The reason this paper
was published in Scienceis that they made this big claim that they saw an
order-of-magnitude more genes that are imprinted, and I don’t think that’s
true,” says Tomas Babak, a computational biologist at Stanford University
in California, who challenged the study in a paper2 published on 29 March.
Dulac counters that she and her team “absolutely stand by those data”,
adding that they have confirmed some of their findings by other means. The
situation resembles an ongoing debate over another RNA-sequencing paper3
published in 2011. In that study, Vivian Cheung of the University of
Pennsylvania in Philadelphia and her colleagues reported evidence that RNA
editing — which creates differences between a gene’s DNA sequence and the
RNA sequence it gives rise to — is “widespread” in the human genome. RNA
editing had been seen before, but the finding that it was so frequent
challenges the central dogma, which holds that an organism’s genes are
transcribed faithfully.
Other scientists have argued that Cheung’s results arose largely from
errors in data analysis and that the true extent of RNA editing is probably
no greater than previously thought4. Cheung did not respond to Nature’s
request for comment on this story, but she has stood by her results.
For their study, Dulac and Gregg used high-throughput RNA sequencing to
search mouse RNA for single nucleotide polymorphisms (SNPs) — one-letter
variations in genetic sequence. The researchers then asked whether the SNPs
they found for each gene could be traced to one or to both parents. If the
SNPs were encoded mainly by one parent’s copy of the gene, the team
concluded that the gene was imprinted (see ‘The silence of the genes’).
Expand
But Babak says that the statistical methods Dulac and Gregg used were not
rigorous enough to rule out false positives. His team used multiple methods
to estimate the false discovery rate — for instance, by applying stricter
criteria for what could be considered instances of imprinting and by
estimating how many spurious examples of imprinting would appear by chance
if mice from identical genetic backgrounds were bred together. Babak’s team
then applied its false discovery rate to Dulac and Gregg’s data and
concluded that most of the instances of imprinting identified in the
original paper were probably false positives. Dulac counters that Babak’s
analysis may be filtering out legitimate but complex instances of imprinting.
“What’s happened in the first few papers on these problems is that the
statistics and analysis in general have not been done very carefully,” says
Lior Pachter, a computational biologist at the University of California,
Berkeley. “And that means you may get completely wrong answers.”
Researchers have had many years to develop standard methods to minimize
errors and biases in DNA sequencing, but such methods are still being
developed for high-throughput RNA sequencing.
Pachter says that another key problem is that high-profile papers in the
field may be well reviewed for their biology but not their computational
foundations. “The culture is not the same in biology as it is in statistics
or math, where reviewers sit with a paper for months, check the statistics
and the math, and run the programs and test them,” he says.
The debate has implications for any sequencing-based study that requires
statisticians to identify rare genetic phenomena using relatively new
methods. “If you don’t deal with the analytical details very carefully,
you’re going to get into trouble because of the low signal-to-noise ratio”
in these types of experiments, says Jin Billy Li, a genomicist at Stanford
University who was one of the critics of Cheung’s RNA-editing paper.
Dulac says that she and her colleagues are now using different statistical
methods to reanalyse the imprinting data, but adds, “I am quite confident
that we will find things that are likely to be around the same order of
magnitude” as originally reported.
Nature
484,
428
(26 April 2012)
doi:10.1038/484428a
http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
RNA studies under fire
High-profile results challenged over statistical analysis of sequence data.
Erika Check Hayden
25 April 2012
Article tools
Download PDF
Rights and Permissions
Share/bookmark
High-throughput RNA sequencing has yielded some unexpected results in the
past few years — including some that seem to rewrite conventional wisdom in
genetics. But a few of those findings are now being challenged, as
computational biologists warn of the statistical pitfalls that can lurk in
data-intensive studies.
The latest case centres on imprinted genes. Humans and most other animals
inherit two copies of most genes, one from each parent. But in some cases,
only one copy is expressed; the other copy is silenced. In such cases, the
gene is described as being imprinted. In July 2010, a team led by Catherine
Dulac and Christopher Gregg, both then at Harvard University in Cambridge,
Massachusetts, published a study1 in Science estimating that 1,300 mouse
genes — an order of magnitude more than previously known — were imprinted.
Now, researchers are arguing that a flawed analysis led Dulac and Gregg to
vastly overestimate imprinting in their paper. “The reason this paper
was published in Scienceis that they made this big claim that they saw an
order-of-magnitude more genes that are imprinted, and I don’t think that’s
true,” says Tomas Babak, a computational biologist at Stanford University
in California, who challenged the study in a paper2 published on 29 March.
Dulac counters that she and her team “absolutely stand by those data”,
adding that they have confirmed some of their findings by other means. The
situation resembles an ongoing debate over another RNA-sequencing paper3
published in 2011. In that study, Vivian Cheung of the University of
Pennsylvania in Philadelphia and her colleagues reported evidence that RNA
editing — which creates differences between a gene’s DNA sequence and the
RNA sequence it gives rise to — is “widespread” in the human genome. RNA
editing had been seen before, but the finding that it was so frequent
challenges the central dogma, which holds that an organism’s genes are
transcribed faithfully.
Other scientists have argued that Cheung’s results arose largely from
errors in data analysis and that the true extent of RNA editing is probably
no greater than previously thought4. Cheung did not respond to Nature’s
request for comment on this story, but she has stood by her results.
For their study, Dulac and Gregg used high-throughput RNA sequencing to
search mouse RNA for single nucleotide polymorphisms (SNPs) — one-letter
variations in genetic sequence. The researchers then asked whether the SNPs
they found for each gene could be traced to one or to both parents. If the
SNPs were encoded mainly by one parent’s copy of the gene, the team
concluded that the gene was imprinted (see ‘The silence of the genes’).
Expand
But Babak says that the statistical methods Dulac and Gregg used were not
rigorous enough to rule out false positives. His team used multiple methods
to estimate the false discovery rate — for instance, by applying stricter
criteria for what could be considered instances of imprinting and by
estimating how many spurious examples of imprinting would appear by chance
if mice from identical genetic backgrounds were bred together. Babak’s team
then applied its false discovery rate to Dulac and Gregg’s data and
concluded that most of the instances of imprinting identified in the
original paper were probably false positives. Dulac counters that Babak’s
analysis may be filtering out legitimate but complex instances of imprinting.
“What’s happened in the first few papers on these problems is that the
statistics and analysis in general have not been done very carefully,” says
Lior Pachter, a computational biologist at the University of California,
Berkeley. “And that means you may get completely wrong answers.”
Researchers have had many years to develop standard methods to minimize
errors and biases in DNA sequencing, but such methods are still being
developed for high-throughput RNA sequencing.
Pachter says that another key problem is that high-profile papers in the
field may be well reviewed for their biology but not their computational
foundations. “The culture is not the same in biology as it is in statistics
or math, where reviewers sit with a paper for months, check the statistics
and the math, and run the programs and test them,” he says.
The debate has implications for any sequencing-based study that requires
statisticians to identify rare genetic phenomena using relatively new
methods. “If you don’t deal with the analytical details very carefully,
you’re going to get into trouble because of the low signal-to-noise ratio”
in these types of experiments, says Jin Billy Li, a genomicist at Stanford
University who was one of the critics of Cheung’s RNA-editing paper.
Dulac says that she and her colleagues are now using different statistical
methods to reanalyse the imprinting data, but adds, “I am quite confident
that we will find things that are likely to be around the same order of
magnitude” as originally reported.
Nature
484,
428
(26 April 2012)
doi:10.1038/484428a
c*h
3 楼
看不动。。。
【在 g****n 的大作中提到】
: 某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
: 自己宿舍门
: 口：今日青春女生，明日成功女性。
【在 g****n 的大作中提到】
: 某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
: 自己宿舍门
: 口：今日青春女生，明日成功女性。
o*r
4 楼
当时RNA editing那篇出来的时候，俺们JC，内部结论就是没啥实质内容，很搞巧的
paper。
paper。
g*l
5 楼
OMG，娘子，快来看1000%的甲醇来了
【在 c********h 的大作中提到】
: 看不动。。。
【在 c********h 的大作中提到】
: 看不动。。。
a*y
6 楼
cool
【在 o********r 的大作中提到】
: 今天的nature news:
: http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
: RNA studies under fire
: High-profile results challenged over statistical analysis of sequence data.
: Erika Check Hayden
: 25 April 2012
: Article tools
: Print
: Email
: Download PDF
【在 o********r 的大作中提到】
: 今天的nature news:
: http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
: RNA studies under fire
: High-profile results challenged over statistical analysis of sequence data.
: Erika Check Hayden
: 25 April 2012
: Article tools
: Download PDF
t*Q
7 楼
今夜加工处理。
贴在
【在 c********h 的大作中提到】
: 看不动。。。
贴在
【在 c********h 的大作中提到】
: 看不动。。。
i*n
8 楼
希望明年我的东西能发表，给这个火上加根柴。
【在 o********r 的大作中提到】
: 今天的nature news:
: http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
: RNA studies under fire
: High-profile results challenged over statistical analysis of sequence data.
: Erika Check Hayden
: 25 April 2012
: Article tools
: Print
: Email
: Download PDF
【在 o********r 的大作中提到】
: 今天的nature news:
: http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
: RNA studies under fire
: High-profile results challenged over statistical analysis of sequence data.
: Erika Check Hayden
: 25 April 2012
: Article tools
: Download PDF
c*h
9 楼
kao,一天不学习，赶不上刘少奇
【在 g***l 的大作中提到】
: OMG，娘子，快来看1000%的甲醇来了
【在 g***l 的大作中提到】
: OMG，娘子，快来看1000%的甲醇来了
X*2
10 楼
类似的文章还有很多。
都是在数学或统计，或是mcmc“近似”计算时出问题。
【在 o********r 的大作中提到】
: 今天的nature news:
: http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
: RNA studies under fire
: High-profile results challenged over statistical analysis of sequence data.
: Erika Check Hayden
: 25 April 2012
: Article tools
: Print
: Email
: Download PDF
都是在数学或统计，或是mcmc“近似”计算时出问题。
【在 o********r 的大作中提到】
: 今天的nature news:
: http://www.nature.com/news/rna-studies-under-fire-1.10502?gobac
: RNA studies under fire
: High-profile results challenged over statistical analysis of sequence data.
: Erika Check Hayden
: 25 April 2012
: Article tools
: Download PDF
m*d
11 楼
女生横批：好好学习
男生横批：天天向上
【在 g****n 的大作中提到】
: 某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
: 自己宿舍门
: 口：今日青春女生，明日成功女性。
男生横批：天天向上
【在 g****n 的大作中提到】
: 某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
: 自己宿舍门
: 口：今日青春女生，明日成功女性。
l*1
12 楼
Sure
进来有些纺锭饥不择食的 数学模型都敢造假喽
please refer:
Math paper retracted because it “contains no scientific content”
Written by ivanoransky
April 17, 2012
According to a retraction notice for “Computer application in mathematics,
” published in Computers & Mathematics with Applications: Read the rest of
this entry »
from
//retractionwatch.wordpress.com/2012/04/17/math-paper-retracted-because-it-
contains-no-scientific-content/#more-7311
更别说生物统计的麻醉学的193篇论文的撤稿的世界记录 可能不久就会被更新吧 Lol
193 papers could be retracted: Journal consortium issues ultimatum in Fujii case
Last month, the journal Anaesthesia published a statistical analysis of Fujii’s research bya UK
anesthesiologist named John Carlisle which cast serious doubt on the veracity of the studies.
//retractionwatch.wordpress.com/2012/04/10/193-papers-could-be-retracted-journal-consortium-
issues-ultimatum-in-fujii-case/#more-7238
再不改革 回到中世纪的那会
A lab 忽悠B lab B lab忽悠C lab Clab 再忽悠A lab
反正都是玄学哦 NGS rna-seq assembly or Stem Cancer Cell GWAS/ SNP
>scientists today to small-business owners, rather than people trying to
satisfy their curiosity about how the world works. “You’re marketing and
selling to other scientists,” she said. “To the degree you can market and
sell your products better, you’re creating the revenue stream to fund your
enterprise.”
//www.nytimes.com/2012/04/17/science/rise-in-scientific-journal-retractions-
prompts-calls-for-reform.html?_r=1
//publicationethics.org/
【在 X******2 的大作中提到】
: 类似的文章还有很多。
: 都是在数学或统计，或是mcmc“近似”计算时出问题。
进来有些纺锭饥不择食的 数学模型都敢造假喽
please refer:
Math paper retracted because it “contains no scientific content”
Written by ivanoransky
April 17, 2012
According to a retraction notice for “Computer application in mathematics,
” published in Computers & Mathematics with Applications: Read the rest of
this entry »
from
//retractionwatch.wordpress.com/2012/04/17/math-paper-retracted-because-it-
contains-no-scientific-content/#more-7311
更别说生物统计的麻醉学的193篇论文的撤稿的世界记录 可能不久就会被更新吧 Lol
193 papers could be retracted: Journal consortium issues ultimatum in Fujii case
Last month, the journal Anaesthesia published a statistical analysis of Fujii’s research bya UK
anesthesiologist named John Carlisle which cast serious doubt on the veracity of the studies.
//retractionwatch.wordpress.com/2012/04/10/193-papers-could-be-retracted-journal-consortium-
issues-ultimatum-in-fujii-case/#more-7238
再不改革 回到中世纪的那会
A lab 忽悠B lab B lab忽悠C lab Clab 再忽悠A lab
反正都是玄学哦 NGS rna-seq assembly or Stem Cancer Cell GWAS/ SNP
>scientists today to small-business owners, rather than people trying to
satisfy their curiosity about how the world works. “You’re marketing and
selling to other scientists,” she said. “To the degree you can market and
sell your products better, you’re creating the revenue stream to fund your
enterprise.”
//www.nytimes.com/2012/04/17/science/rise-in-scientific-journal-retractions-
prompts-calls-for-reform.html?_r=1
//publicationethics.org/
【在 X******2 的大作中提到】
: 类似的文章还有很多。
: 都是在数学或统计，或是mcmc“近似”计算时出问题。
c*o
13 楼
其实不算成功，应该反过来：今日成功女性，明日青春女生。
这样才是完美人生。
【在 g****n 的大作中提到】
: 某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
: 自己宿舍门
: 口：今日青春女生，明日成功女性。
这样才是完美人生。
【在 g****n 的大作中提到】
: 某大学女生宿舍贴了一对联：今日青春女生，明日成功女性...一男生照抄一遍，贴在
: 自己宿舍门
: 口：今日青春女生，明日成功女性。
b*w
14 楼
RNA Editing 那篇是有serious flaw的。很多mapping的artifect都没有排除。
c*7
15 楼
高！！高！！实在是高！！！
l*1
16 楼
这个网页不错
htp://rafalab.jhsph.edu/688/
title:
R programming of Biostatistics for Genomics
from Statistics for Genomics Online Lecture (Spring 2012)
Johns Hopkins School of Public Health
htp://rafalab.jhsph.edu/688/
title:
R programming of Biostatistics for Genomics
from Statistics for Genomics Online Lecture (Spring 2012)
Johns Hopkins School of Public Health
p*w
17 楼
服了U
【在 c*******o 的大作中提到】
: 其实不算成功，应该反过来：今日成功女性，明日青春女生。
: 这样才是完美人生。
【在 c*******o 的大作中提到】
: 其实不算成功，应该反过来：今日成功女性，明日青春女生。
: 这样才是完美人生。
c*o
18 楼
服了就发包子吧。
【在 p*********w 的大作中提到】
: 服了U
【在 p*********w 的大作中提到】
: 服了U
p*w
19 楼
这个是斑大赤裸裸对版民的勒索啊
【在 c*******o 的大作中提到】
: 服了就发包子吧。
【在 c*******o 的大作中提到】
: 服了就发包子吧。
h*y
20 楼
niu!
【在 c*******o 的大作中提到】
: 其实不算成功，应该反过来：今日成功女性，明日青春女生。
: 这样才是完美人生。
【在 c*******o 的大作中提到】
: 其实不算成功，应该反过来：今日成功女性，明日青春女生。
: 这样才是完美人生。
r*g
21 楼
不是一样的吗？不明白/
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