Failures of citation based rating - new analysis

Ramy Aziz, one of the most enthusiastic members of the PLoS ONE Editorial Board has very nicely commented on a recently published PLoS ONE article which highlights the failures of the so called 'impact factor' based rating of the value of science journals. The journal impact factors were released last week itself and thus the analysis presented in the article is very timely, indeed. Below are Ramy's comments to which I agree 100%:

"The presented results pertain to what we believe to be the largest and most thorough survey of usage- and citation based measures of scientific impact."

I agree with the above statement and I definitely like this thorough comparison of a large number of "impact measures." The article is also informative and has introduced in detail many methods for evaluation of scientific literature with which I was not familiar.

However, on reading the article, I had the following concerns regarding its reliability:

1) Most of the readers will only read the abstract, especially because the article is full of statistical and technical terms. The conclusion of the abstract is not so informative and poorly represents the insightful discussion at the end of the article.
In particular, I would have preferred a positive than a negative conclusion. I would have preferred a recommendation of which measures correlate better with each of the multiple dimensions of scientific attributes (e.g., quality, prestige, impact, immediacy, etc.) rather than the--rather obsolete--conclusion that JIF is not optimal and should be "used with caution." I have read more than 20 articles and editorials (including those in Science, JBC, JCI, PLoS) written in the past two years and stating that JIF should be used with caution.

2) I agree with the authors that JIF is misused; however, a value cannot be blamed for what it does not stand for. I believe the authors have given more importance to JIF (probably because of its "impact" on the scientific community), and I think that this has affected the objectiveness of the paper.

3) As the authors state in the introduction, until now I'm not sure whether how "scientific impact" is defined. Is it "journal impact", "article impact", or "scientist impact"? And which of these matters more? However, the authors seem to have committed the same unfair comparison that JIF and SJR do: measuring articles, scientists, and even "science" itself by the journals rather than by the articles. Journal-level metrics simply mean that an article is evaluated mostly prior to its publication. Once a scientist "makes it to Science or Nature," he or she celebrates even if the article will never be cited again!

4) Once more I declare my agreement with the authors that JIF is neither the most accurate nor the fairest way to measure scientists, articles, or even journals. However, this "conclusion" is clearly stated in the introduction (quoted below). Why the analysis then?

"The JIF is now commonly used to measure the impact of journals and by extension the impact of the articles they have published, and by even further extension the authors of these articles, their departments, their universities and even entire countries. However, the JIF has a number of undesirable properties which have been extensively discussed in the literature [2], [3], [4], [5], [6]. This had led to a situation in which most experts agree that the JIF is a far from perfect measure of scientific impact but it is still generally used because of the lack of accepted alternative"

5) One final concern/question.
Citation-based metrics take into consideration journals that are technologically behind (for many "non-science-related" reasons, including funding problems, poor management, being published in a developing country, etc.) and thus do not have well established web sites but are still citable and cited. Do the "usage-based metrics" just ignore those journals?

Need for qualitative assessment of biomedical research

Here comes a new PLoS ONE article describing one of the most authoritative analyses of the research impact - by none other than the Wellcome Trust. The research conducted by experts of the Trust summates that authoritative opinions about a published research finding constitute important benchmark of the quality of biomedical research. These data vindicate stand of the advocates of post publication peer review (and I am one humble volunteer) that modern day qualitative indicators are extremely necessary to judge the impact of biomedical research findings. Not only that this article supports and strengthens cause of the 'Faculty of 1000' but also that of PLoS ONE, although indirectly. The latter is no doubt the most successful forerunner of the idea of post-publication peer review and qualitative assessment while harnessing the web2.0 based semantic tools for such purposes. At this critical juncture, it is time for the concerned institutions to retrospect about their practices of evaluating research productivity of scientists based on bibliometric indices (such as the 'impact factor') alone.

PLoS ONE Prokaryotic Genome Collection - now launched

I am excited to tell you of the latest collection of some of the high-impact articles, the PLoS ONE Prokaryotic Genome Collection. Liz Allen of PLoS, has some more things to say …read her full blog post here.

There is an editorial overview that accompanies the new collection; it’s written by me. Comments related to the collection and the ‘overview’ have started to trickle in, such as this one by Dr Ramy Aziz:

“This article lists very interesting challenges and questions that will be answered in the next decade of this millennium. With the revolution stirred by next-gen sequencing machines, sequencing/resequencing steps have become quick and cheap. Thus, data generation is the least part to worry about. However, as the article appropriately discusses, the problem is what to sequence and then how to make sense out of the piles.

We will very soon have 5,000 fully sequenced prokaryotic genomes, but, as quick annotation tools are being developed, we realize very well that more genomes annotated = more errors propagated.

In addition to high-speed and high-performance …” … Read more here.

Evidence of Leprosy in Ancient India

In a recent PLoS ONE article, Gwen Robbins and colleagues reported analysis of a 4000-year-old skeleton from India, which represents both the earliest archaeological evidence for human infection with Mycobacterium leprae in the world and the first evidence for the disease in prehistoric India. I think the authors need to have clear definitions of 'ancient origins' and 'historic presence'. Leprosy has clear origins from Africa as for tubeculosis (TB). After spreading from Africa the disease may have assumed endemic potentials in certain countries such as India. Therefore, the findings here should be consistent with our own research, published back in 2006 about TB, wherein we suggested that India was a historic cradle for mycobacterial infections and that she served as an ancient corridor for an early worldwide spread of TB. The authors did not cite our work; may be an oversight! But, I am more concerned that they as well forgot to refer to an important PLoS ONE paper which recently attempted to characterize about 9000 year old skeletons from submerged, ancient burials in Israel using paleopathology and DNA based evidence.

How to get cited one hundred times?

Exactly 2 years ago, PLoS ONE published this superb article (Fahlgren N, et al., 2007 High-throughput sequencing of Arabidopsis microRNAs: Evidence for frequent birth and death of MIRNA genes. PLoS ONE 2: e219), a citation classic. Thanks to its being published via Open Access, today it crossed the landmark of one hundred citations in Google Scholar. The paper thus became one of the star articles of PLoS series and the first one from PLoS ONE to log 3 digit citations in a record time of 2 years. The article was also evaluated in F1000 Biology and its corresponding author interviewed at PLoS blog.

Novel ‘replication check mechanism’ key to dormant Tuberculosis

Tuberculosis is a major communicable disease expanding globally and is caused by Mycobacterium tuberculosis (M. tb). The disease is a main killer among infectious diseases in the world with the occurrence of 2 million deaths each year and 8 million cases of active disease. The biggest challenge of tuberculosis (TB) is its ability to survive in dormant form in apparently healthy individuals for decades. M.tb, the diehard pathogen that causes tuberculosis, is capable of staying asymptomatically in a latent form, persisting for years in very low replicating state, before getting reactivated to cause active infection.

M.tb is known to survive for extended periods during the latency phase without any replication. During this phase the bacterium senses the surrounding environmental conditions such as availability of nutrients, immune cell preponderance etc. and if needed puts its machinery back in action to grow and replicate. The regulation of chromosomal DNA replication therefore is a very important switch to maintain dormancy. While the bacterium is dormant replication is bare minimum.

A new study published by PLoS ONE (In-vitro helix opening of M. tuberculosis oriC by DnaA occurs at precise location and is inhibited by IciA like protein) provides some fresh insights into maintenance of dormancy by the pathogenic mycobacteria. Professor Seyed E. Hasnain (Distinguished Professor at the Institute of Life Sciences at the Hyderabad University campus, Hyderabad, India) who led the study said ‘the dormant state of the bacterium is maintained by a novel protein called as Inhibitor of Chromosomal initiation (IciA), which our group has rigorously characterized and which binds to the A+T rich region of the origin of replication’. ‘This binding blocks helix opening of the A+T rich region, a step critical for chromosomal replication initiation to occur’ says Hasnain. This represents the first evidence that chromosomal DNA replication control is a critical molecular switch in the form of IciA protein, which the TB bacteria over express to remain dormant.

Besides identification of the replication check phenomenon by the IciA, the study also generated an in vitro model of mycobacterial replication which will be a very important tool in the hands of infection biologists trying to understand intricacies of microbial acquisition, survival and adaptation under different stress conditions and in different hosts. Although the present study largely represents laboratory based observations, direct evidence for the role of the IciA like protein will come from M.tb iciA knockout experiments to be performed in an animal infection model. While such experiments are underway at Hasnain labs, it will be interesting to see if quantitative expression of IciA in tuberculosis patient’s material could effectively be harnessed as a molecular marker of M.tb activation.

Songs that thronged PLoS ONE through 2008

Well, we listened a lot to bird songs last year at PLoS ONE forums and journal clubs. After birds, mice arrived on the scene to sing and squeal, meaning that rodents could as well joyfully sing, and that their songs to prospective mates are as likely complex as those of birds. However, unlike birds, their vocalizations are discharged at ultrasonic frequencies, and that is why no one noticed them, nor was anyone motivated to celebrate them. But, as one of the many celebrated PLoS ONE stories (DOI: 10.1371/journal.pone.0001893) echoes in popular media and blogosphere, we may hope they will likely find a place in romantic poetry! The article was published by H. Wang and colleagues quite some time back (in April 2008), but was recently showcased in a recent news round-up by New Scientist of the top ten genetics stories of the year. Alison Motluk of New Scientist discussed this research and also provided recordings of the squeaks of male mice in a human audible format.

“Most musical, most melancholy bird,” said Samuel Taylor Coleridge of the nightingale ‘but whether birdsong can affect us in the same way as a beautiful sonata played by a human musician is another matter’ said Rebecca Walton in her blog post summating another celebrated article by Stefan Koelsch of the University of Sussex, wherein his team, investigated differential response to instrumental and computerised music. According to this research, volunteers who listened to recordings of professional pianists showed more emotional activity of the brain than did those who listened to recordings made by computer. This article was covered in different headlines by the Chronicle of Higher Education (Don't Cry For Me, R2D2), The Telegraph (Sweaty music find could help develop new treatments), The Guardian (Music that brings a tear to the eye), Wired (Study: Computer Musicians Ain't Got No Soul) and PsychCentral (Computer Music Not As Calming).

At the end of the year, one more article ("Practicing a musical instrument in childhood is associated with enhanced verbal ability and nonverbal reasoning" PLoS ONE, 2008) dominated the blogosphere, this time for another reason, to celebrate the second birthday of PLoS ONE! This was all about an excellent blog by SciCurious of the Neurotopia 2.0 (Einstein was smart, but Could He Play the Violin?) who won the PLoS ONE second birthday synchroblogging competition organized on December 20, 2008.

All content published in PLoS ONE, from dinosaurs to elephants to chimps to birds to bats and about mice to butterflies and bees is freely available online. Rate them and comment and discuss yourself to enjoy the full power of Web 2.0 technology that PLoS ONE harnesses. Here at PLoS ONE is certainly quite diverse food for thought and you can always join in the discussion by creating an account on the journal site and posting your comments for others to read.

New PLoS ONE articles evaluated at F1000 Biology

It appears that the year 2008 is closing on a good note - in the last 6 days three important articles from PLoS ONE were evaluated by the F1000 Biology faculty. These articles were graded as significantly novel reports (see below).

Rapid SNP discovery and genetic mapping using sequenced RAD markers. Baird NA, Etter PD, …, Cresko WA, Johnson EA PLoS ONE 2008 3(10):e3376

Evaluated by: Tony Long on December 23, 2008

F1000 Factor: 6.0 (Must Read)

If I were you: perceptual illusion of body swapping. Petkova VI, Ehrsson HH PLoS ONE 2008 3(12):e3832

Evaluated by: Aina Puce on December 19, 2008

F1000 Factor: 6.0 (Must Read)

The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways. Fukada T, Civic N, …, Superti-Furga A, Hirano T PLoS ONE 2008 3(11):e3642

Evaluated by Bruce Pitt on December 18, 2008

F1000 Factor: 9.0 (Exceptional)

All PLoS ONE content is freely available on the web and readers could themselves rate and evaluate the articles. However, those evaluated on F1000 are certainly the crème de la crème kind of material; at any given time about 4% of the PLoS ONE articles are evaluated at the F1000.

A PLoS ONE article that is hot favourite of F1000 Editors

Last month I evaluated on F1000 an article from PLoS ONE that addressed infection as a driving force for the extinction of rats native of Christmas Island. The importance of this timely study was also discussed on BLoG ONE. Apparently, it appears that the F1000 evaluation of this article has been taken on quite a good note. It just appeared in the latest issue of the F1000 update wherein the Editors of F1000 reinforce the opinion that the PLoS ONE paper indeed provides important evidence that infectious diseases are a potential cause of future extinctions of endangered mammalian species. The original article is freely available for anyone to read, rate and comment.

Good-bye CDFD

Finally, today I said good-bye to CDFD, the institute where I worked for more than 10 years. It has been a wonderful experience being there and having enjoyed each and every moment of a busy scientific career. The University of Hyderabad, my new employer, extended a warm welcome also to my advocacy of Science 2.0, PLoS ONE and Open Access in general. Change is for the betterment - lets see how true.

The first case of mammalian extinction due to an exotic disease – an alarm bell for conservation efforts?

An interesting article that we accepted last month for PLoS ONE describes a very fine DNA detective work to put forth the hypothesis of mammalian extinction due to an introduced infectious disease. The research published on November 6 suggests that a century ago the black rat species, which led to the emergence of the bubonic plague in Medieval Europe and considered one of the worst invasive species on the planet, sheltered a parasitic disease that eliminated two immunologically naive rat species native to the Christmas Island in the Indian Ocean.

Alex Greenwood from the Old Dominion University in Norfolk, Virginia, and colleagues brilliantly attempted to solve the mystery of the mammalian extinctions. They collected samples from 21 historical rat specimens from Christmas Island stored at natural history museums across the United Kingdom. These researchers analyzed preserved remains of black rats, the extinct species, and the crosses of the two. The century old specimens were then analyzed for genetic signatures of crossbreeding as well as for the presence of Trypanosoma lewisi, the close relative of the sleeping sickness pathogen, T. evansii.

The interesting part of the story is that the authors argue they did not find any evidence of hybridization between black rats and Christmas Island rats. They emphasize that mere invasion does not necessarily lead to extinction and, that on Christmas Island, the Christmas Island shrew survived until 1985 even in the presence of black rats, arguing against general competitive exclusion or predation. Therefore, it appears that their data are more consistent with disease as a reason for extinction rather than competition.

The authors speculate that the extinction of Christmas Island rats (Rattus macleari) was due to a trypanosome pathogen present in fleas carried by black rats introduced to the island (Rattus rattus). The study presents acceptable evidence for the presence of trypanosome infection in the Christmas Island rats after black rats have been introduced to the island, but not before.

However, if we consider some of the arguments, the scenario becomes little implausible - Trypanosome diseases do not normally have short and acute progression and T. lewisi (which the authors tested for) is not reported to be acutely pathogenic in rats. The other question could be - what is the reason to believe that the Christmas Island rats would reveal a different pathology compared with the black rats which were putatively carrying the disease? Nevertheless, it is possible that R. macleari would have been immunologically naïve to black rat pathogens which acted more deadly in a naïve host compared to its natural host or to a host adapted to it. But the next argument could be - why the Christmas Island rats were not killed by some other pathogen (for example a rodent virus) introduced by the black rats? Also, it is possible that the authors missed a possible interspecific ecological competition that might have served as an important extinction force. But no one knows ways to test that!

Leaving this debate to the scientific community (and the PLoS ONE readership at large) to choose among different explanations, I thought the paper was indeed worthy of publication because some of the emerging and re-emerging infectious diseases could possibly serve as a strong force to future extinctions, especially of the wildlife that are increasingly threatened and we thus have a warning bell in the form of this important study.

The Cancer Week - Nagoya: Paradigm shift in Japanese Science Communication

Traditionally, a majority of the Japanese researchers and clinicians have been shying off the mainstream communication skills in science and technology. However, this seems fast becoming history. The Japanese Cancer Association (JCA) meeting, a grand annual event in cancer science and medicine, started this year with a new trend – compulsory communication in English!

The cancer week witnessing the annual congregations of the JCA and the Japan Society for Clinical Oncology began on October 27 this year in Nagoya. The twin meeting was attended by 5000 attendees comprising of cancer specialists, doctors, basic researchers and students. Reportedly, for the first time in the last 66 years’ history of the Japanese cancer meetings, it was made compulsory for the presenters to write their abstracts in English only and 12 dedicated International sessions (with English only presentations) were organized. Also, the aspects of World Cancer Declaration were presented for the want of advocacy and solidarity of the Japanese cancer community to the cause of global cancer prevention.

This new beginning has also made possible for International academics and doctors to participate and communicate through the platform of JCA. It was especially a great opportunity for me to have shaped, participated and chaired one of their international sessions. This was also a nice platform for Open Access advocacy and I was excited to note the growing interest of Japanese biosciences community towards OA journals in general and PLoS ONE in particular.

The next JCA meeting is planned in Tokyo in 2009. Let us hope it will be equally successful and rewarding.

TB and Mycobacteria community publishes in PLoS ONE

Tuberculosis (TB) continues to cause increasing deaths globally and last year alone about 1.7 million lives were lost (The World Health Organization, 2006). The human immunodeficiency virus (HIV) epidemic has worsened the situation as the incidence rates dramatically jumped in recent times (http://www.globalhealthfacts.org). Most countries that are crippled by the menace of TB have negligible flow of international funding for research and new fruits of post genomic discovery are yet to percolate to these zones. Library budgets are seriously dwindling and the researchers, clinicians and higher degree students have no access to TB research that has been traditionally published in ‘closed access’ journals. I recall my days (1997) at the National Dairy Research Institute, Karnal (India), where, I had to run on almost weekly basis to the National Medical Library in Delhi (100 Kilometers) or to the library of the Post Graduate Institute of Medical Research (PGI) at Chandigarh (~100 Kilometers) to refer to some of the 'print only' journals for my dissertation work on TB. The situation has not improved much even today. Thankfully, Open Access publishing has arrived as the new ray of hope for many who hold dear to their hearts the cause of poverty alleviation through epidemic control. PLoS ONE has been seriously partnering this cause since its inception in 2006 and has since then published about 73 landmark articles addressing the broad areas of TB control, mycobacterial biology and medicine. We at PLoS ONE are overwhelmed with this response of the TB and mycobacteria community and thank the authors who opted for the journal to showcase their research and to widen access to those who desperately need it - the developing world. In particular, it is quite pleasing for me to put on record the patronage extended by the mycobacterial research community from India by publishing highest number of papers on the topic from a high burden country.

Exciting and noteworthy in PLoS ONE: My picks

There are 62 brand new articles published at PLoS ONE this week which certainly reflects quite diverse food for thought. You can always join in discussion on interesting articles by creating an account on the journal site and posting your comments for others to read. Also, you may like to rate the articles. Ratings are the quickest and easiest way for users to indicate their support for the authors and to highlight which articles are of potential impact for the readers and the community. I suggest why not to begin with these exciting ones?

Dinosaurian Soft Tissues Interpreted as Bacterial Biofilms:

A scanning electron microscope survey was initiated to determine if the previously reported findings of "dinosaurian soft tissues" could be identified in situ within the bones. The results obtained allowed a reinterpretation of the formation and preservation of several types of these "tissues" and their content. Mineralized and non-mineralized coatings were found extensively in the porous trabecular bone of a variety of dinosaur and mammal species across time. They represent bacterial biofilms common throughout nature. Biofilms form endocasts and once dissolved out of the bone, mimic real blood vessels and osteocytes. Bridged trails observed in biofilms indicate that a previously viscous film was populated with swimming bacteria. Carbon dating of the film points to its relatively modern origin. A comparison of infrared spectra of modern biofilms with modern collagen and fossil bone coatings suggests that modern biofilms share a closer molecular make-up than modern collagen to the coatings from fossil bones. Blood cell size iron-oxygen spheres found in the vessels were identified as an oxidized form of formerly pyritic framboids. Our observations appeal to a more conservative explanation for the structures found preserved in fossil bone.

Remodeling of the Streptococcus agalactiae Transcriptome in Response to Growth Temperature

To act as a commensal bacterium and a pathogen in humans and animals, Streptococcus agalactiae (group B streptococcus, GBS) must be able to monitor and adapt to different environmental conditions. Temperature variation is a one of the most commonly encountered variables. To understand the extent to which GBS modify gene expression in response to temperatures encountered in the various hosts, we conducted a whole genome transcriptome analysis of organisms grown at 30°C and 40°C. We identified extensive transcriptome remodeling at various stages of growth, especially in the stationary phase (significant transcript changes occurred for 25% of the genes). A large proportion of genes involved in metabolism was up-regulated at 30°C in stationary phase. Conversely, genes up-regulated at 40°C relative to 30°C include those encoding virulence factors such as hemolysins and extracellular secreted proteins with LPXTG motifs. Over-expression of hemolysins was linked to larger zones of hemolysis and enhanced hemolytic activity at 40°C. A key theme identified by our study was that genes involved in purine metabolism and iron acquisition were significantly up-regulated at 40°C. Growth of GBS in vitro at different temperatures resulted in extensive remodeling of the transcriptome, including genes encoding proven and putative virulence genes. The data provide extensive new leads for molecular pathogenesis research.

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI). S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the ΔsimA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development. Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine.

Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis

The functional equilibrium between natural regulatory T cells (Treg) and effector T cells can affect the issue of numerous infections. In unvaccinated mice, the influence of Treg in the control of primary infection with mycobacteria remains controversial. Here, we evaluated the role of Treg during prophylactic vaccination with Mycobacterium bovis BCG (Bacillus Calmette-Guérin) on the induction of T cell responses and on the protective effect against subsequent M. tuberculosis challenge in mice. We demonstrated that, subsequent to BCG injection, Treg were recruited to the draining lymph nodes and negatively control anti-mycobacterial CD4+ — but not CD8+ — T-cell responses. Treatment of BCG-immunized mice with an anti-CD25 mAb (PC61) induced an increase IFN-γ response against both subdominant and immunodominant regions of the protective immunogen TB10.4. In Treg-attenuated, BCG-immunized mice, which were then infected with M. tuberculosis, the lung mycobacterial load was significantly, albeit moderately, reduced compared to the control mice. Our results provide the first demonstration that attenuation of Treg subset concomitant to BCG vaccination has a positive, yet limited, impact on the protective capacity of this vaccine against infection with M. tuberculosis. Thus, for rational design of improved BCG, it should be considered that, although the action of Treg does not represent the major cause of the limited efficiency of BCG, the impact of this cell population on the subsequent control of M. tuberculosis growth is significant and measurable.

Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing

Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.

100th PLoS ONE article evaluated at Faculty of 1000 Biology

As a part of its thematic focus for the month of July, PLoS ONE announced a call for papers addressing gene expression studies. It appears that the gene expression community has already embraced PLoS ONE in a great style - here appears the authoritative and insightful review [by Charles Auffray] of one of the gene expression articles published by PLoS ONE: ‘High throughput gene expression measurement with real time PCR in a microfluidic dynamic array’. Interestingly, Auffray’s is the 100th evaluation of PLoSONE articles at the Faculty of 1000 Biology.

Below is the simplified version of Charles Auffray’s evaluation of the article. Full evaluation can be read at F1000Biology website.

‘The novel microfluidic device described in this paper transforms real-time quantitative PCR into a much higher throughput technology for gene expression measurement. The authors have used a dynamic array of microfluidic channels, valves and nanoliter reaction chambers to perform simultaneously 2304 real-time qPCR assays, monitoring expression of 45 human genes in 18 tissues with very high sensitivity (down to <10 RNA molecules). The results presented compare very well with those obtained with conventional microliter RT-PCR, outperforming DNA microarrays. Miniaturization and parallelization result in faster delivery of results with much less reagents and handling. This technological advance should prove useful for validation of expression profile signatures obtained with microarrays, and their extensive use for diagnosis and prognosis. In order to compete directly with microarrays for transcriptome analysis, the number of genes that can be assayed in parallel would have to be increased by at least two orders of magnitude’.

Of its 2600 articles in PubMED, one hundred (4%) articles have been already evaluated and commented upon by F1000 Members. For a broad based and high volume journal such as PLoS ONE, the F1000 evaluations constitute important quality indexes for individual articles apart from hundreds of articles already reviewed through PLoS ONE’s unique rating and discussion tools and journal clubs which are fully compliant to the cutting edge concepts of Science 2.0. Such 'article level metrics' are especially relevant when the significance of a popular bibliometric index, the 'impact factor' is increasingly being questioned.

Conflict of interest: I volunteer as Section Editor of PLoS ONE and as a Faculty Member at F1000 Biology and F1000 Medicine.

Thematic Journal Clubs at PLoS ONE

I liked the idea at PLoS ONE to have a thematic focus each month to assess how well the journal is doing in that particular area. This is gauged most often with the help of statistics obtained from Google Analytics on page views related to each article in that category and the most accessed article is highlighted on the main page of the journal. At this stage PLoS ONE receives from the authors of the article their comments on the editorial processes and their feelings on seeing the article fetching community attention/response. Also, the article receives at this occasion additional comments from experts and young scientists in the academia through PLoS ONE's unique discussion and response forum with ratings and annotations. This can effectively catalyze community engagement through PLoS ONE Journal Clubs (JCs). Such JCs involve groups of scientists, post docs and graduate students who volunteer to discuss PLoS ONE articles and post their discussions as a series of questions, comments, annotations, and ratings eventually triggering discussions within a broader scientific community.

New in PLoS ONE: Genetic structure of Adi tribes of North-East India

PLoS ONE today published a crop of 60 brand new articles, several of them are hitting the headlines. An interesting article from India by TS Vasulu and colleagues is also being talked about a lot since this morning (see below). The paper discusses 'Microsatellite based analysis of the genetic status of Adi tribes of Northeast India'.

Population biologists and anthropologists have been traditionally interested in aspects of human history and population migration in India -a homeland of a large number of genetic lineages of tribals and mainstream populations which speak 1600 different languages and dialects.

The article by Vasulu presents important genetic data from a number of closely related Tibeto-Burman speaking tribes from north-east India. The authors correctly present this region of India of utmost importance with respect to ancient human migration processes. In addition, the novel results obtained from these populations are compared with similar data from a range of other populations obtained from the literature.

Based on 15 autosomal microsatellite (STR) markers, the authors studied the genetic affinity, differentiation and sub-structuring among six Adi subgroups, as well as their genetic affinity with other neighbouring, Tibeto-Burman-speaking, tribes of India and with the linguistically divergent east and south-east Asian populations, with whom they share common ethno-historical and cultural attributes. The researchers investigated to what extent the six Adi subgroups are genetically divergent or affiliated. A comparison with the 16 Tibeto-Burman-speaking tribes of the neighbouring region in northern and north-eastern parts of the country as revealed by the cluster analyses indicates geographically proximate populations forming a close cluster. This is to be expected if these populations have indeed diverged from a common source after their settlement in different regions of the country in the recent past. In a comparison of the 50 populations (including populations from east and south-east Asia) for genetic diversity based on the autosomal loci, the resultant clustering tree showed some of the Tibeto-Burman tribes clustering with the populations from Tibet and China and whereas other Tibeto-Burman tribes of India cluster with linguistically different Southeast Asian populations. These results support the possibility that Tibeto-Burman populations were derived from more than one common source. Overall, the Adi and other Tibeto-Burman speaking populations of India are regionally well differentiated and exhibit genetic affinity with the neighboring populations of East/Southeast Asia, based on their shared ethno-history. However, a clearer picture may well emerge from the analysis of increased number of informative genetic markers and from the uniparental markers like mitochondrial DNA and Y chromosome.

You can read the news coverage about this study here and you may post your own reactions and comments directly on the article of Vasulu and colleagues by creating an account on the PLoS ONE website.

[Source: Press release of T S Vasulu, Indian Statistical Institute, Kolkata, India]

Recent PLoS ONE Evaluations at the Faculty of 1000 Biology

This week, 4 new articles from PLoS ONE have been tagged at the F1000 Biology. The articles have been judged as conveying significantly novel observations:

1) The molecular diversity of freshwater picoeukaryotes reveals high occurrence of putative parasitoids in the plankton. Lefèvre E, Roussel B, Amblard C, Sime-Ngando T. PLoS ONE 2008 3(6):e2324

Selected by: Carlos Pedrós-Alió, Instituto de Ciencies del Mar, Spain [ECOLOGY]
Evaluated 24 Jun 2008

Tags: Confirmation, Hypothesis
F1000 Factor: 3.0

Comments:
This paper proposes that parasitism plays a larger role than previously thought in aquatic microbial food webs. This has implications for both the natural history of microorganisms and for carbon flow. Molecular surveys of microbial diversity of aquatic systems regularly provide many sequences related to organisms that are known to be parasites. This paper presents another example of this from a freshwater lake. About 65% of the sequences obtained belonged to Alveolates, Stramenopiles and Fungi. Many of the known organisms in these groups are either parasites or saprotrophs and their abundance suggests they must have a significant role in carbon flow. It is true that molecular surveys overestimate organisms with a large copy number of the 18S rRNA gene and that similarity of sequence does not necessarily imply the same function. However, the proposal of a "parasite loop" within the microbial food web is a welcome stimulus to try to quantify this process in ecosystems.
[Why not rate this article yourself?]

2) The yeast Tor signaling pathway is involved in G2/M transition via polo-kinase. Nakashima A, Maruki Y, Imamura Y, Kondo C, Kawamata T, Kawanishi I, Takata H, Matsuura A, Lee KS, Kikkawa U, Ohsumi Y, Yonezawa K, Kamada Y. PLoS ONE 2008 3(5):e2223

Selected by: Joe Heitman with Cecelia Shertz and Maria E. Cardenas, Duke University Medical Center, United States of America [MICROBIOLOGY]
Evaluated 23 Jun 2008

Tags: Hypothesis, New Finding, Novel Drug Target
F1000 Factor: 3.0

Comments:
The ubiquitous Tor nutrient sensor cascade was discovered to evoke G2/M cell cycle transition via the polo-like kinase Cdc5 in Saccharomyces cerevisiae. It was known that inhibition of Tor with rapamycin causes a G1 cell cycle arrest, whereas these new findings by Nakashima et al. demonstrate that disruption of the Tor complex 1 (TORC1) provokes a G2/M delay. This effect is attributable to TORC1-protein phosphatase 2A mediated Cdc5 nuclear import, which has multiple mitotic roles including Swe1 phosphorylation which controls G2/M transition, cytokinesis, and CLB2 expression. This study reveals Tor is active throughout the cell cycle via key cell cycle regulators. This scenario differs from that found in Schizosaccharomyces pombe, where rapamycin stimulates mitotic entry {1}. Future studies should address if TORC1 governs the G2/M transition in multi-cellular eukaryotes such as humans. Reference: {1} Petersen et al. Nat Cell Biol 2007, 9:1263-1272.
[Why not rate this article yourself?]

3) Patterns of genome evolution among the microsporidian parasites Encephalitozoon cuniculi, Antonospora locustae and Enterocytozoon bieneusi. Corradi N, Akiyoshi DE, Morrison HG, Feng X, Weiss LM, Tzipori S, Keeling PJ. PLoS ONE 2007 2(12):e1277

Selected by: Joe Heitman with Soo Chan Lee, Duke University Medical Center, United States of America [MICROBIOLOGY]
Evaluated 20 Jun 2008

Tags: Hypothesis, New Finding
F1000 Factor: 3.0

Comments:
Genomic inspection for three microsporidians, obligate intracellular eukaryotic pathogens, reveals a high degree of synteny conserved in their otherwise reduced, compact, rapidly evolving genomes. Comparative genomic analysis between the completed Encephalitozoon cuniculi genome (2.9 Mb) with corresponding representative segments (~429 kb) from the genomes of Antonospora locustae and Enterocytozoon bieneusi reveals a high degree of gene conservation across all three, despite considerable evolutionary distance, but with less frequent changes in higher scale genomic architecture. The microsporidia were once thought to be ancestral eukaryotes devoid of a mitochondria, but with the discovery that they harbor a mitochondrial relic (the mitosome), it is now appreciated that they are highly evolved eukaryotes that emerged either from within the fungi or as a sister group to fungi. Their genomes have been compacted, not only by rampant gene loss, but also by the loss of repetitive sequences and transposons, a purging of nearly all introns, by a shortening of each protein by an average of 15%, and by virtue of having very short intergenic regions. While their gene sequences have been evolving at an accelerated pace, their higher order genome architecture has become constrained, likely as a consequence of the shortened intergenic regions, which limits the translocations that can occur without disrupting neighboring gene structure or expression. As a consequence, syntenic genomic relationships, rather than phylogenetic sequence relationships, represent a novel window on their evolutionary trajectory.
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4) Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(pos)CD25(high) T cells for immunotherapy. Peters JH, Hilbrands LB, Koenen HJ, Joosten I PLoS ONE 2008, 3(5):e2233

Selected by: Mohamed Sayegh with Jessamyn Bagley, Brigham and Women’s Hospital and Children’s Hospital Boston, United States of America [IMMUNOLOGY]
Evaluated 19 Jun 2008

Tags: Tech Advance
F1000 Factor: 3.0

Comments:
The authors describe an efficient protocol for the generation of antigen-specific human regulatory T cells (Treg). This may advance the goal of using Treg to generate specific tolerance to antigens, such as those present on organ allografts.
[Why not rate this article yourself?]

Faculty of 1000 Biology is a new revolutionary literature evaluation service which helps researchers identify most significant and impacting publications in their field. Evaluations at the F1000 are considered as authoritative insights on individual articles. Being on F1000 I always enjoyed to analyze how post publication evaluations of articles might throw up a new bibliometric tool to gauge the worth of individual articles. While keeping a tab on this , I can say that the Faculty of 1000 Members are increasingly inclined to evaluate high quality Open Access articles from journals such as PLoS ONE. Thanks to the fact that these articles are reader (and media) friendly and picked easily by the F1000 Faculty. It is evident from the fact that nearly 100 articles from PLoS ONE have been evaluated there between January 2007 and June 2008. This boolean search may be helpful to track PLoS ONE evaluations at the F1000 Biology as compared to evaluations from journals such as Nature.

New PLoS ONE evaluations at Faculty of 1000 Biology

On April 21, Michael Symonds from the University of Nottingham evaluated at the F1000Biology a very recent article published in PLoS ONE (Unique environmental effects on physical activity participation: a twin study. Duncan GE, Goldberg J, Noonan C, Moudon AV, Hurvitz P, Buchwald D PLoS ONE 2008 3(4):e2019). He rated this article with the F1000 factor of 3.00; this value denotes that the article is of interest to community in the corresponding research area and that he recommends it to be referred to.

Here are the evaluator's specific remarks:

"As with all aspects of human health and behaviour, the relative influence of genes versus environment looms large. This novel twin study strongly suggests that environmental, rather than genetic, factors are the main determinants of physical activity participation. One way in which this study differs from others in the field is the threshold level of physical activity, which may explain its apparently surprising results."

Another PLoS ONE article (The Cayman crab fly revisited--phylogeny and biology of Drosophila endobranchia. Stensmyr MC, Stieber R, Hansson BS. PLoS ONE 2008 3(4):e1942) was evaluated by Artyom Kopp of University of California. The faculty has recommended this article to be read by the community members in the corresponding research area and has rated the article with the F1000 factor of 3.00.

This article reports rediscovery of Drosophila endobranchia, a fruit fly that lives in the mouth of land crabs on the Caribbean Island of Grand Cayman and that was last sighted in 1966. The evaluators’ specific comments on the article are here:

“This paper will revive the interest in a very unusual species of Drosophila that feeds on the secretions of land crabs - D. endobranchia from the Grand Cayman Island. Following up on Hampton Carson's work, the authors describe the ecology and behavior of this species and determine its phylogenetic position. Drosophila, while commonly known as "fruit flies", exploit a wide variety of food sources, and crab feeding in particular has evolved at least three times in different Drosophila lineages”.

Separate to this, the article has enjoyed a lot of media attention in the last few days.

Roughly about 5% of PLoSONE articles are evaluated on the Faculty of 1000 at a given time, which coincides to fourth position in terms of number of evaluations, after Science (~17% of the published articles evaluated), Nature (~15% of the published articles evaluated) and PNAS (~15% of the published articles evaluated).

PS: F1000Biology is available to subscribers only. All major research institutions across the world already subscribe to the service. All contents at F1000 are usable through the creative commons attribution license unless otherwise stated.

Welcome the 2000th article of PLoS ONE

Thanks to the Open Access movement, PLoS ONE (PONE) shall be publishing its 2000th article in a few hours from now. This is perhaps becoming a special moment for all those linked to the success of this wonderful publishing project. I think the credit goes to its managers, an overwhelmingly efficient editorial board, thousands of qualified referees who respond to a fast peer-review process and a seamless electronic workflow.

Having said that, I feel it’s getting almost a norm to listen about PONE’s strides and therefore, I can’t say how festive this occasion is going to be! …happening and burgeoning, going from strength to strength in such a short period of not even 2 years, PONE is often making (and breaking) records.

This reminds me of a shouting blog post when PONE published its 500th paper in just 25 weeks of its launch. Soon after, the 1000th article was accepted on September 20, 2007. Although the corresponding blog post was not that shouting, it mentioned the article acceptance was chosen to match another special occasion - birthday of Chris Surridge, first Managing Editor of PONE. What a special birth day gift!
… it will be interesting to know whose birthday coincides with 2000th PONE article!