Neuroscience sees the light

Posted on 25 Nov 2009 by Daniel Evanko

After many years of steady but seemingly slow progress, the development and use of light-based methods for investigating the function of the brain is really accelerating. Part of this is undoubtedly due to the excitement surrounding the use of light-activated channels for neuronal stimulation. This has been highlighted as one of our “”https://www.nature.com/nmeth/focus/moy2008/index.html#mtw">Methods to Watch" for the past two years. But probe development has also overcome some big hurdles recently, from the bolus loading of small calcium dyes to the development of genetically-encoded calcium indicators capable of providing usable signals in living animals.

An editorial in the December issue discusses the advances taking place in optical probes for measuring neuronal function and calls for the use of more standardized procedures for evaluating new probes.

Nature Methods has been requiring a basic set of evaluation tests on new fluorescent proteins that we publish for a few years now and it is possible we could try and do something similar for genetically-encoded sensors but this would obviously be complicated by the greater complexity of sensors and the fact that they respond to different stimuli and have diverse applications.

We encourage the community to tell us what they think about the value and feasibility of standardized tests for new fluorescent probes and sensors.

Nature Methods is 5 years old!

Posted on 29 Sep 2009 by Daniel Evanko

It’s hard to believe that five years have gone by since Veronique Kiermer, Nicole Rusk and myself saw the first issue of Nature Methods go out the door. In some ways it doesn’t feel like it was that long ago while in others it feels like much, much longer. But it has certainly been a rewarding and stimulating five years and we are thrilled with the success that Nature Methods has enjoyed.

To help celebrate, Veronique asked a local pastry shop run her friend called “”https://www.howsweetitispastry.com">How Sweet It Is" to bake a cake using the cover image of our inaugural issue. It turned out spectacularly and tasted just as good. I’m hoping to convince Veronique to post a blog entry describing the undertaking with accompanying pictures.

While our readers won’t be able to taste the cake, they can see a picture of it in its full glory (minus a slice) on the cover of the October issue. Below, I have pasted an image of the October 2009 cover next to an image of our October 2004 cover so you can see how well the artisans recreated our first cover.

Our readers can however, enjoy a special selection of content in our special anniversary issue. Science Historians Angela Creager and Hannah Landecker provide fascinating Historical Commentaries on the roles methods have played in 20th Century biological science. We are also indebted to Steven Shapin for his help in pointing us to these two people, without whom the issue wouldn’t be as special as it is.

Of course we must also thank the practicing scientists who wrote the scientific commentaries on a selection of methodological topics that have appeared in Nature Methods over its first five years. While we would have liked to include more topics, this limited selection illustrates quite well how Nature Methods has participated in conveying important methodological developments to our readers. For a full description of the special commentaries in the issue please see the editorial.

Finally, we would like to thank all our authors, reviewers and readers for their support over the years. We hope everyone enjoys this special issue and we look forward to another five years of communicating methodological advances.

Voting for the Method of the Year now even easier

Posted on 22 Sep 2009 by Daniel Evanko

To help prevent automated spamming of the Method of the Year voting we require that anyone wishing to vote be a registered user of nature.com . Unfortunately, the regular nature.com registration required answering quite a few questions and it is quite likely that some people would rather not bother.

We have now done away with all the questions. All you need to do is provide a username and password and you can immediately log in and begin voting. We hope this will encourage more people to participate and vote for their choice of Method of the Year.

Top downloads for August ’09

Posted on 06 Sep 2009 by Daniel Evanko

A paper describing a potential new pipeline for structural genomics based on small angle X-ray scattering was far and away the most popular paper of the August issue. It will be very interesting to see what kind of impact it has on the field. While it may not provide high-resolution structures like x-ray crystalography, it is certainly faster and has a higher success rate, both of which are critical parameters for high-throughput pipelines. A paper from Helicos describing new terminator nucleotides for single-molecule next-generation sequencing (or should this be 2nd or 3rd generation?) made it to the #5 spot.

Top 7 research papers published in the August issue

1. Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS)

2. Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human

3. Mass spectrometry of membrane transporters reveals subunit stoichiometry and interactions

4. SHOREmap: simultaneous mapping and mutation identification by deep sequencing

5. Virtual terminator nucleotides for next-generation DNA sequencing

6. Global discovery of adaptive mutations

7. Metabolic network analysis integrated with transcript verification for sequenced genomes

The top five spots in the ten most popular papers published prior to our August issue and downloaded during August are unchanged since last month. We have a surprise appearance of an old and slightly controversial paper at position #6. This appearance appears to be the result of their publication of a follow-up paper in PNAS at the beginning of August. Squeaking in at #9 and #10 are two papers from the July issue. The top downloaded paper in July was also close behind but didn’t quite make it.

Top 10 research papers published prior to the August issue

1. Mapping and quantifying mammalian transcriptomes by RNA-Seq

2. mRNA-Seq whole-transcriptome analysis of a single cell

3. Universal sample preparation method for proteome analysis

4. Stem cell transcriptome profiling via massive-scale mRNA sequencing

5. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency

6. The development of a bioengineered organ germ method

7. Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing

8. Stable knockdown of microRNA : in vivo: by lentiviral vectors

9. In vivo fluorescence imaging with high-resolution microlenses

10. Mapping the structure and conformational movements of proteins with transition metal ion FRET

Next-generation naming

Posted on 06 Sep 2009 by Daniel Evanko

What wasn’t to like when people started talking about ‘next-generation’ sequencing? It sounds so cutting edge and futuristic. But now what?

‘Next-next-generation’ and the inevitable ‘next-next-next-generation’ bring back memories of MAPKK and MAPKKK except that those had intrinsic meaning to them that were obvious to the reader; thus, they worked.

Recently, people have started using the terms ‘second generation’ to refer to the 454, Illumina and SOLiD sequencing platforms and ‘third generation’ to refer to the Helicos and PacBio platforms. Nanopore-based platforms may also qualify for the ‘third generation’ moniker.

But while the acronym NGS was readily adopted by people to refer to next-generation sequencing, SGS and 2GS just haven’t seen the same kind of uptake in the community as acronyms for second-generation sequencing. For some reason they just aren’t as visually satisfying. Eventually, I think one of these will be picked up and popularized. While neither may be beautiful (if that can be said for any acronym), either of them would be infinitely better than NNGS and, heaven forbid, NNNGS.

Is rare always real?

Posted on 28 Aug 2009 by Daniel Evanko

Deep sequencing of metagenomic datasets by next-generation technology, has revealed a richness and diversity of microbial species that far exceeded previous expectations.

In 2006 Mitchell Sogin presented the concept of a rare biosphere, low-abundance microbial populations that have persisted over large evolutionary time scales. Sogin described it as a ‘potentially inexhaustible reservoir of genomic innovation’ which lets microbial communities recover from environmental assault and allows them to adapt to changed circumstances.

How do scientists determine microbial diversity? Sequence reads covering the hypervariable regions of 16S rRNA genes are often used for classification. These ‘pyrotags’ (named thus since they are obtained on Roche’s 454 sequencer) can be classified by matching them against a rRNA sequence database.

The challenge is that for most microbial species the 16S rRNA gene is not known. An alternative is shotgun sequencing and grouping of reads into operational taxonomic units; i.e. a cluster of sequences with a defined difference to a neighboring cluster — commonly a sequence difference of 3% is required at the species level, 5% at the genus level.

But with predictions of an ever larger rare biosphere voices of caution are starting to be heard saying that its size is overestimated. Is everything that is classified as a new and rare species indeed real, or simply a sequencing error?

Most recently we featured an error correction program in our own pages that addressed this issue; and a note of caution by Phil Hugenholtz and colleagues about ‘Wrinkles in the rare biosphere’ just appeared in “Early View” in Environmental Microbiology.

How well founded are the concerns of an artificially inflated rare biosphere? Are current estimates of the rare biosphere really 10-fold too high? If so, what are the consequences — does it mean that the rare biosphere is far less important than assumed? Is it not such an inexhaustible reservoir after all but just background noise?

We understand that these are very controversial issues and we would love to hear from you.

Metagenomics versus Moore’s law

Posted on 28 Aug 2009 by Daniel Evanko

Moore’s law refers to the trend observed in computing hardware that the number of transistors on a computer chip doubles about every two years, thus effectively doubling computing power. This has been considered quite a rapid increase.

However, this increase pales in comparison to recent and continuing advances in the throughput of DNA sequencing technology that have resulted in an astonishing increase in the production of DNA sequence by biologists. This is certainly true in the field of metagenomics which involves shotgun sequencing of the genomes (or transcriptomes) of all the organisms in an environmental sample. Biologists are adopting this technology at an rate that was completely unanticipated by most people in the field. This is creating a situation where comprehensive analysis of the resulting sequences, whose analysis is far more complex than for single-genome sequence, is becoming computationally intractable with existing resources and pipelines. The Joint Genome Institute’s call for large scale (Terabase) "Grand Challenge” metagenomic projects highlights the scale of datasets that people are now discussing.

The editorial in the September issue of Nature Methods discusses this situation and calls for concerted efforts to ameliorate the metagenome-analysis gridlock that appears imminent. The recently formed M5 (metagenomics, metadata, metaanalysis, multiscale-models and metainfrastructure) Consortium will be proposing a promising solution, the ‘M5 Platform’, later this year. We hope these efforts will find support and be successful at ensuring this deluge of valuable data is analyzed efficiently and productively.

Delay in delivery of Nature Methods in Italy

Posted on 21 Aug 2009 by Daniel Evanko

Our print subscribers in Italy will unfortunately experience a delay in receiving their print copies of the August edition of Nature Methods. Regretably, all 2,000 copies delivered to Italy were stolen and haven’t been recovered. We are working to have the issue reprinted and delivered as soon as possible.

We often receive comments from our print subscribers that their copy of Nature Methods tends to get pilferred from their mailbox or desk but we certainly never expected to witness a theft of this scale. We are doubtful that demand for the journal is such that a black market has developed for copies at cut-rate prices but it is humorous to imagine what the culprits response was when they opened the boxes.

Top downloads for July ’09

Posted on 09 Aug 2009 by Daniel Evanko

Two Correspondences made the list of top downloads for July coming in at #3 and #4, demonstrating that while this format may not report new methods it does have information of high interest to readers. The two top downloads seem to highlight a high level of interest in assaying single cells and using FRET to examine protein dynamics.

Top 8 research papers published in the July issue

1. Quantitative analysis of gene expression in a single cell by qPCR

2. Mapping the structure and conformational movements of proteins with transition metal ion FRET

3. Limitations and possibilities of small RNA digital gene expression profiling

4. Enabling IMAC purification of low abundance recombinant proteins from E. coli lysates

5. In vivo fluorescence imaging with high-resolution microlenses

6. Protein interaction platforms: visualization of interacting proteins in yeast

7. Agouti C57BL/6N embryonic stem cells for mouse genetic resources

8. Reaching the protein folding speed limit with large, sub-microsecond pressure jumps

There has been very little movement in the ten most popular papers published prior to our July issue and downloaded during July. The exception is the appearance of the HUPO test sample paper from June appearing at #7. The papers below this have changed but mostly because a large number of papers have very similar download numbers and they shuffle around from month to month.

Top 10 research papers published prior to the July issue

1. Mapping and quantifying mammalian transcriptomes by RNA-Seq

2. mRNA-Seq whole-transcriptome analysis of a single cell

3. Universal sample preparation method for proteome analysis

4. Stem cell transcriptome profiling via massive-scale mRNA sequencing

5. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency

6. Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing

7. A HUPO test sample study reveals common problems in mass spectrometry–based proteomics

8. Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon

9. Amplification-free Illumina sequencing-library preparation facilitates improved mapping and assembly of (G+C)-biased genomes

10. A versatile tool for conditional gene expression and knockdown

Naming scientific software

Posted on 30 Jul 2009 by Daniel Evanko

The editorial in the August issue of Nature Methods discusses an issue that comes up when computational biologists—or anyone else for that matter—wants to report a novel algorithm that biologists may want to use in their research. Specifically, whether or not to supply a named software implementation of their algorithm that biologists can use.

As part of our standard material sharing policy, Nature Methods generally requires that authors provide a useable software program implementing any new algorithm that is integral to a method they’re reporting. But we have never said anything about naming the software.

It recently came to our attention that there are a number of factors that act to discourage authors of new algorithms from naming a software implementation of their algorithm. As discussed in the editorial, this can lead to difficulties later on and in many cases providing a name for the software has benefits that outweigh the potential hazards. Read the editorial and then let us know what you think.

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