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A Tale of Disputed Research Results Ends Badly

The sad and sobering tale of how allegedly fabricated results of research led by a Johns Hopkins University lab led to the suicide of a scientist in Taiwan,and the dismissal of the man who blew the whistle, are the focus of a feature in yesterday's Washington Post.

The story is the tale of Daniel Yuan, formerly a genetics researcher in Jeff Boeke's lab at Hopkins. For years, Yuan suggested that data being generated in the lab's studies of gene interactions in yeast were suspicious.

Yuan was dismissed from Hopkins in 2011, and last summer one of the members of the research team, Yu-yi Lin, was found dead in his new lab in Taiwan of an apparent suicide.

Lin was an author of a paper published in Nature last year that now, according to the Washington Post, may soon be corrected by the journal. At age 38, Lin left behind a wife and three daughters.

The article suggests that Yuan was fired because of his concerns that the data that was used to write the Nature paper and others did not support the conclusions reported. Yuan also reached out to the editors at Nature, warning the journal of the weakness of the data behind the paper, saying that its results were overstated and that some of the analyses outlined in the paper may not have been conducted at all.

After Lin was found dead, Yuan received an e-mail "essentially blaming him for driving Lin to suicide," the Post reports.

The Post feature also suggests that the saga of Yuan and Lin are part of a larger trend of falsified research and unfounded research conclusions being published because of the immense pressure caused by an increasing number of scientists who are racing to win grants in an environment of diminishing funding.

March 13, 2013

An 'Omics Orchestra

An orchestra with a sick tuba player and a lead violinist who is missing her bow — this is how Reinhard Hiller, co-director of South Africa's Center for Proteomic and Genomic Research sees the state of genomics and proteomics in Africa today. Writing on CPGR's blog, Hiller describes a situation on the continent where investments made in human resources are not sustained as top scientists often emigrate for better employment opportunities, infrastructure is mismanaged and isolated, and countries compete against each other rather than developing a regional strategy for success. "The net effect is that investments into physical and human resources don't yield proper returns in terms of scientific publications, patents, and biomedical innovation," Hiller writes.

According to Hiller, the solution to these challenges is network orchestration, the "art of assembling an array of resources into seamless strings of value generation." He says that African genomics and proteomics infrastructure should be reassembled in an "agile, customer-focused fashion" based on principles of "network, cooperation, and coordination." With alternative resources built into the resulting network, Hiller says that African genomics and proteomics infrastructure would also be "resilient to external and internal turbulence." In addition, Hiller says that Africa is particularly poised to benefit from network orchestration. "Where else, if applied properly, can these principles have more positive impact than in a resource-scarce environment, such as in many of the emerging economies in Africa?" he writes.

March 13, 2013

The HeLa Difference

HeLa cells are ubiquitous in biomedical research — indeed, there have even been reports of HeLa cells contaminating and taking over other cell lines in the lab. By sequencing and transcriptomic analyses, researchers from the European Molecular Biology Laboratory and University Hospital Heidelberg report in G3: Genes, Genomes and Genetics that a number of pathways in HeLa cells "exhibit significantly different expression patterns from those in normal human tissues."

The researchers, led by EMBL's Lars Steinmetz, performed DNA and RNA sequencing of a HeLa Kyoto cell line and examined its mutational profile and gene expression levels, finding about 4.5 million SNVs and half a million indels. The cell line also exhibits an extensive amount of chromosomal rearrangements to the point of chromothripsis, the researchers add. In addition, about 2,000 genes are expressed at a higher level in the HeLa cell line than in normal tissue, and those genes appear to mainly be involved in proliferation, transcription, and DNA repair. "The high expression of some DNA repair genes, some of which also carry potentially damaging NS mutations, suggests that even though HeLa displays high chromosomal instability, specific DNA repair mechanisms may be activated, perhaps irrespective of their effectiveness," the researchers write.

"Our study underscores the importance of accounting for the abnormal characteristics of HeLa cells in experimental design and analysis, and has the potential to refine the use of HeLa cells as a model of human biology," Steinmetz adds in a statement.

March 13, 2013

NSF's New Acting Director

ScienceInsider reports that the US National Science Foundation has tapped Cora Marrett, a sociologist and academic administrator, to serve as its acting director after current head Subra Suresh steps down on March 22 until a permanent replacement is appointed and confirmed.

Suresh is vacating the role after holding it for two and half years to become the president of Carnegie Mellon University.

Marrett is the deputy director of the NSF, a post she's occupied since 2009. This isn't the first time that she has managed the institution while its leadership changed hands, according to the article. She was in charge in between the departure of former head Arden Bement in May 2010 and Suresh taking over in October of the same year. She's also run education programs and headed up the NSF's social and behavioral sciences directorate.

ScienceInsider adds that some former directors say Marrett should take over the role on a permanent basis, though it notes that only one deputy has become director throughout the agency's history.

March 13, 2013

This Week in Genome Biology

Researchers from the US and France used comparative genomics to begin defining the core and accessory genomes of nitrogen-fixing root nodule bacteria from a genus called Sinorhizobium. The team started by sequencing and assembling draft genomes for four dozen strains representing five so-called genospecies: S. meliloti, S. medicae, S. fredii, S. saheli, and S. terangae. From there, they compared sequences across the strains, particularly with respect to each strain's capabilities and preferred host plants. "The diversity of genes present in the accessory genomes of members of [the Sinorhizobium] genus indicates that each bacterium has adopted slightly different strategies to interact with diverse plant genera and soil environments," the University of Minnesota's Michael Sadowsky and colleagues say.

A study led by the University of Bristol's Seirian Sumner looks at transcriptional profiles contributing to primitive forms of eusocial insect behavior. Together with colleagues from the UK, Spain, and Switzerland, Sumner (who was based at the Zoological Society of London while the research was carried out) performed transcriptome sequencing on brain tissue from tropical paper wasps representing different social castes. The group's results indicate that the brain transcriptomes of worker wasps tend to be more active those of queen wasps, showing particularly pronounced expression differences at uncharacterized genes. For more on the study, check out GenomeWeb Daily News.

A team from Germany and the US describes work done delineating a de novo assembly of the newt transcriptome. The researchers turned to Sanger, Illumina, and Roche 454 sequencing techniques to assemble RNA sequences representing nearly 121,000 non-redundant transcripts for the red spotted newt, Notophthalmus viridescens, an amphibian with large, complicated, and yet-unsequenced genome. Among the newly assembled sequences were more than 800 transcripts that appear to be specific to the urodeles — an order that includes newts, salamanders, and other amphibians that regenerate limbs or tissues — suggesting some of these transcripts may contribute to the regeneration process. "Our data provide the groundwork for mechanistic experiments to answer the question [of] whether urodeles utilize proprietary sets of genes for tissue regeneration," they write.

GWDN has more on that study, here.

March 13, 2013

The Human Tree

The human family tree is complicated and only getting more complex as researchers like Harvard Medical School's David Reich unearth evidence hidden in the genome of interbreeding — not just between different human populations, but between humans and other hominins, writes Carl Zimmer at Discover magazine.

For a while, researchers traced the spread of people out East Africa to Europe and beyond, supplanting the Neandertals that had lived in Europe. But then they noticed that some stretches of the human genome from certain populations looked a bit like the Neandertal genome. "We were suspicious of the result," Reich tells Zimmer. "We found signals of mixture and then worked very hard to make them go away." But they eventually concluded that about 2.5 percent of the human genome from European and Asian populations is from Neandertals.

Making things more complex was the discovery of a new hominin line, now called the Denisovans. While there appears to be no overlap in the genomes of the Denisovans and Europeans, Africans, or Asians, pieces of the Denisovan genome were found in Australian Aborigines and the Mamanwa people from the Phillipines.

And the picture may become even more complicated, as there could be other hominins out there waiting to be discovered and analyzed. "The world is full of things like Denisova Cave," Reich tells Zimmer. "There must be thousands of other bones out there."

March 12, 2013

Science Smarts

They've been narrowed down to 40 finalists, and this evening the winners of the 2013 Intel Science Talent Search will be announced. As the New York Times notes, the judges look at more than the projects the students have been working on. "Our goal is to find future leaders in science," David Marker, the chair of the judges' panel and a math professor at the University of Illinois at Chicago, tells the Times.

Among the finalists are Jacob Johnson from Boxborough, Mass., whose project used both bioinformatic and experimental techniques to identify genes that may drive breast cancer; Sara Volz from Colorado Springs, Colo., used artificial selection to increase oil yields from algae; and Mayuri Sridhar from Kings Park, NY, developed a computer model of how mutations to p53 lead it to lose its cancer-suppression ability.

March 12, 2013

Patents and Diagnostics

Intellectual property claims may hinder using genomic tools for the betterment of public health, particularly for combating non-communicable diseases like type 2 diabetes, writes Anna George, an adjunct professor at Murdoch University in Australia and a Chatham House associate fellow, at the Guardian Professional. She estimates that about 20 percent of the human genome "is subject to patents that can impose complex legal and cost constraints on medicines and diagnostics."

Current — though not universal — practices allow the patenting of unmodified, though isolated, bits of genomic DNA, George says, noting that there are legal challenges, especially focused on Myriad Genetics' BRCA1 and BRCA2 gene patents, underway in the US and Australia. Two reports, one from the US National Academy of Sciences and the other from the Department of Health and Human Services, indicate that patent restrictions could hinder the development of diagnostics, George adds.

"Ensuring open access to such basic scientific genomic data is a necessary step to enable the scientific collaboration and inventive solutions to evolve," she says. "The so-called 'genome divide' is not just between developed and developing countries but also between closed and open access to these unique produces of nature that no one invented."

March 12, 2013 / 2 comments

This Week in PNAS

An international team led by investigators in France outlines efforts to sequence and characterize the genome of the red algal species Chondrus crispus, commonly called Irish moss — a member of a lineage descended from the first photosynthetic eukaryotes formed through endosymbiosis. After using Sanger sequencing to tackle a C. crispus sample grown from material collected in Peggy's Cove, Nova Scotia, in the 1980s, the researchers delved into the 105 million-base-pair genome sequence, identifying 9,600 or so predicted protein-coding genes. Between the metabolic pathways in the genome, the overall gene set, and features of the genome such as gene density and intron-exon patterns, the team got clues about everything from Irish moss biology to the nature of ancestral marine plants.

In another early, online study, researchers uncovered epigenetic contributors to the facial tumor disease that has sharply cut wild Tasmanian devil numbers. A University of Cambridge and University of Tasmania-led group found evidence suggesting the contagious tumor disease dodges devils' immune systems by tinkering with histone marks that normally manage antigen processing and expression of major histocompatibility complex class I molecules on infected cell surfaces. "These results demonstrate how [devil facial tumor disease] passes as an allograft, revealing characteristics that may be important in the emergence and evolutionary success of contagious cancers more generally," researchers write. "Further, these results have implications for the development of a vaccine against [devil facial tumor disease]."

Our sister publication GenomeWeb Daily News has more on the study, here.

A research trio based at the University of California, San Diego, describes algorithms for finding sites in the tumor genome that contain chromosomal abnormalities caused by a breakage-fusion-bridge, or BFB, mechanism. The researchers came up with computational approaches designed to see two features stemming from BFB — a type of genomic instability that begins when a chromosome loses a telomere, making it prone to fusion followed by DNA breaks during cell division. The group demonstrated the feasibility of using these approaches to detect BFB using simulated data and sequence data representing seven previously tested pancreatic cancer samples.

March 12, 2013

Case Review

The US National Science Foundation is examining suspected cases of plagiarism among its funded grant applications, ScienceInsider reports. An audit by the agency's inspector general office of all 8,000 funded proposals from fiscal year 2011 with plagiarism-detecting software uncovered about 100 instances of suspected plagiarism. "My group is now swamped," James Kroll, the head of administrative investigations in that office, tells ScienceInsider.

Further, Allison Lerner, the NSF inspector general, recently told a congressional panel that the number of allegations of research misconduct has tripled during the last decade, ScienceInsider adds. "The acceptable rate for me should be zero. The IG's results indicate that it's very important to train everybody … so we can bring that rate down," Subra Suresh, the NSF director, says.

March 11, 2013

Hopeful Sequence

Lilly Grossman had been suffering from painful muscle twitches that would wake her up multiple times a night, preventing both her and her parents from sleeping soundly for the past 13 years, writes Ed Yong at Not Exactly Rocket Science. After participating in Sarah and Eric Topol's Idiopathic Diseases of Man, or IDIOM, study — as part of which Lilly and her parents had both their genomes and exomes sequenced — researchers found mutations in two of Lilly's genes. "The team suspects that ADCY5 accounts for Lilly's shaking, while DOCK3 influences her balance and muscle weakness. It seems that she was born with extraordinary bad luck—a double-whammy of fresh mutations in two separate genes that conspired to produce her unique constellation of problems," Yong writes.

This did, though, suggest a possible treatment, and while that treatment hasn't been a cure, the frequency and severity of Lilly's tremors have lessened, Yong notes. "Treatments aren't going to be instantaneous or 100 percent, but they're hope," Steve Grossman, Lilly's father, tells Yong. "We gained hope. And the more data we have, the better position we'll be in to figure this out."

March 11, 2013

How to Deal

The Committee on Publication Ethics is holding a virtual forum tomorrow focused on "text recycling," or self-plagiarism. Self-plagiarism, or duplication, is a common reason for retractions, adds Ivan Oransky at Retraction Watch. "Such duplication retractions are so common that we don't get to most of them," he notes.

COPE, a group comprised of academic journal editors, says that "opinions are divided as to how much text overlap with an author's own previous publications is acceptable, and editors often find it hard to judge when action is required." It adds that editors from BioMed Central have drawn up some guidelines on the matter to help spark discussion.

While the BioMed Central guidelines note that "editors should consider each case of text recycling on an individual basis," they add that "duplication of data is likely to always be considered serious."

The response to duplicated text, the guidelines add, should vary depending on the severity of the overlap and whether it was detected before or after publication. For example, the guidelines note that if a minor overlap is detected before publication, the authors may merely be asked to re-write that section and cite the paper they drew upon. However, if most of a discussion section is re-used, and it is detected after publication, editors should, according to the guidelines, retract the article.

March 11, 2013 / 2 comments

This Week in PLOS

In PLOS One, researchers report on a genetic analysis of a 33,000-year-old dog skull found in a cave in Siberia's Altai Mountains. A team from the US, Russia, Finland, and Spain performed targeted mitochondrial DNA sequencing on jaw bone and tooth samples from the skull, showing that these samples matched one another and clustered genetically with domestic dogs. The aged canine remnants shared fewer genetic similarities with modern-day wolves or with ancient wolves from the Pleistocene period whose remains were recovered from the same cave. "These results suggest a more ancient history of the dog outside of the Middle East or East Asia," authors of the study say, "previously suggested as centers of dog origin."

For more on the study, check out a related story in our sister publication GenomeWeb Daily News.

Complex traits are often a consequence of common variants falling across many genes, according to a PLOS Genetics study. Researchers from Australia and Korea assessed genotyping data for almost 7,200 individuals from Korea, using a combination of genome-wide estimation and partitioning analyses to look at how well sets of common SNPs explained 49 complex traits — from obesity and blood pressure to liver, lung, and kidney functions. For almost all of the traits tested, SNPs spread across the genome seemed to explain a considerable proportion of the trait's heritability, pointing to widespread polygenicity among complex human traits, study authors argued. "Despite examples where a few variants explain a substantial amount of variation," they say, "all these results are consistent with polygenicity being ubiquitous for most complex traits."

A team from Nigeria and Israel cataloged vector-borne pathogens found in Nigerian dogs and three tick species that pester them for a study in PLOS Neglected Tropical Diseases. The researchers used targeted PCR sequencing to track down vector-borne pathogens in blood and tick samples taken from 181 dogs in Nigeria. The analysis uncovered a wide range of pathogens known for infecting either animals or humans, they note, with around 63 percent of the ticks and more than three-quarters of the dogs apparently carrying at least one vector-borne pathogen.

March 11, 2013