By now you have probably checked out our most recent selection of Research Highlights in our November issue. Here are some other interesting methods papers up for consideration that we weren’t able to feature in the journal.

Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators

PNAS 106, 15651 – 15656 (2009)

The yeast Wsc1 cell surface sensor behaves like a nanospring in vivo

Nature Chemical Biology 5, 857 – 862 (2009)

Genetic address book for retinal cell types

Nature Neuroscience 12, 1197 – 1204 (2009)

Protein quantification across hundreds of experimental conditions

PNAS 106, 15544 – 15548 (2009)

Biocompatible Functionalized Polyglycerol Microgels with Cell Penetrating Properties

Angewandte Chemie International Edition 48, 7540 – 7545 (2009)

Single-molecule sequencing of an individual human genome

Nature Biotechnology 27, 847 – 850 (2009)

Cell-selective metabolic labeling of proteins

Nature Chemical Biology 5, 715 – 717 (2009)

Generation of Functional Eyes from Pluripotent Cells

PLoS Biology 7, e1000174 (2009)

RNA–MATE: a recursive mapping strategy for high-throughput RNA-sequencing data

Bioinformatics 25, 2615 – 2616 (2009)

Targeted capture and massively parallel sequencing of 12 human exomes

Nature 461, 272 – 276 (2009)

Sensitive digital quantification of DNA methylation in clinical samples

Nature Biotechnology 27, 858 – 863 (2009)

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.

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.

We hope you’ve had a chance to check out our selection of Research Highlights in the September issue. In addition, you might find the following list of methods papers from the last few months to be intriguing.

Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes

Nature Medicine 15, 967 – 973 (2009)

Determination of protein structural flexibility by microsecond force spectroscopy

Nature Nanotechnology 4, 514 – 517 (2009)

Development of GFP-based biosensors possessing the binding properties of antibodies

PNAS 106, 11895 – 11900 (2009)

Quantification of the yeast transcriptome by single-molecule sequencing

Nature Biotechnology 27, 652 – 658 (2009)

Partial sequencing of a single DNA molecule with a scanning tunnelling microscope

Nature Nanotechnology 4, 518 – 522 (2009)

Virtual taphonomy using synchrotron tomographic microscopy reveals cryptic features and internal structure of modern and fossil plants

PNAS 106, 12013 – 12018 (2009)

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.

Our August issue went live last week; check out the Research Highlights section for a few “news” stories about interesting new methods described in the literature over the last month or two. Unfortunately we cannot highlight every interesting methods paper we find in the pages of the journal, so check out some of the others we considered that didn’t quite make the cut.

Proteomic analysis of S-nitrosylation and denitrosylation by resin-assisted capture

Nature Biotechnology 27, 557-559 (2009)

Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

Science 324, 1210-1213 (2009)

Validated germline-competent embryonic stem cell lines from nonobese diabetic mice

Nature Medicine 15, 814-818 (2009)

Unfolding Individual Als5p Adhesion Proteins on Live Cells

ACS Nano, 3, 1677-1682 (2009)

Development of aliphatic biodegradable photoluminescent polymers

PNAS 106, 10086-10091 (2009)

Directing cell motions on micropatterned ratchets

Nature Physics 5, 606-612 (2009)

Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding

Genome Research, published online 22 June 2009

Twin-spot MARCM to reveal the developmental origin and identity of neurons

Nature Neuroscience 12, 947-953 (2009)

The establishment of gene silencing at single-cell resolution

Nature Genetics 41, 800-806 (2009)

DNA relaxation dynamics as a probe for the intracellular environment

PNAS 106, 9250-9255 (2009)

Interactive exploration of chemical space with Scaffold Hunter

Nature Chemical Biology 5, 581-583 (2009)

Bioactivity-guided mapping and navigation of chemical space

Nature Chemical Biology 5, 585 – 592 (2009)

Two years ago we decided we wanted to do something each year to celebrate the importance of new methodological developments in biological research, and the people who bring them to fruition. In 2007, it was clear that next-generation sequencing was going to have a profound impact on scientific research. Therefore, it was an obvious first choice when we decided to start selecting a ‘Method of the Year’.

Last year we invited our readers to help us in the selection of the Method of the Year 2008 by nominating and voting for their choice. While participation was good, it wasn’t high enough to have much impact on our choice. This year we are starting voting a month earlier and are hopeful that the level of participation will be substantially higher.

We also want to clarify that we are not asking people to nominate and vote for papers published in Nature Methods. Although anyone who wants to nominate a Nature Methods paper is welcome to do so, we hope that readers will consider the broader universe of biological research methods.

It is quite likely that our choice will not be a method represented by a single paper but rather a class of methods like next-generation sequencing or super-resolution imaging. But readers are welcome to pick a single paper that represents a broader methodological advance they want to nominate and explain their choice to other readers.

We have already seeded the voting with our Methods to Watch from the last two years. Maybe one of them will now be ready to be declared Method of the Year.

As always, we welcome your feedback and encourage you to vote for the method you think deserves to be declared the Method of the Year 2009 and encourage your colleagues to do so as well. Just go to https://www.nature.com/nmeth/votemoy2009 and start voting!

Our July issue went live last week, and as always, it includes our popular Research Highlights section. Here is a list of some interesting methods papers we considered (which were published over the last month or two) but were not able, because of space reasons, to cover in the journal.

Metastable Pluripotent States in NOD-Mouse-Derived ESCs

Cell Stem Cell 4, 513-524 (2009)

A Small Molecule Primes Embryonic Stem Cells for Differentiation

Cell Stem Cell 4, 416-426 (2009)

Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4

PNAS 106, 8912-8917 (2009)

Diversity and Complexity in DNA Recognition by Transcription Factors

Science 324, 1720-1723 (2009)

Efficient siRNA delivery into primary cells by a peptide transduction domain–dsRNA binding domain fusion protein

Nature Biotechnology 27, 567-571 (2009)

Mixing and Matching Detergents for Membrane Protein NMR Structure Determination

JACS 131, 7320-7326 (2009)

GPIomics: global analysis of glycosylphosphatidylinositol-anchored molecules of Trypanosoma cruzi

Molecular Systems Biology 5:261 (2009)

Metatranscriptomics reveals unique microbial small RNAs in the ocean’s water column

Nature 459, 266-269 (2009)

Shifted Transversal Design smart-pooling for high coverage interactome mapping

Genome Research 19, 1262-1269 (2009)

Identification of protein O-GlcNAcylation sites using electron transfer dissociation mass spectrometry on native peptides

PNAS 106, 8894-8899 (2009)

Matrix-Free Formation of Gas-Phase Biomolecular Ions by Soft Cluster-Induced Desorption

Angewandte Chemie 48, 4162-4165 (2009)

Antigenic protein modifications in Ehrlichia

Parasite Immunology 31, 296-303 (2009)

Some readers may recall that we ran a cover on our January 2008 issue with an error that keen readers picked up immediately. After that experience we were pretty certain that some readers would question our use of what appears to be a common house fly on our current cover, instead of Drosophila melanogaster, the topic of several papers in the issue. Our keen-eyed readers have indeed noticed the discrepancy and notified us by email or posted about it on their blog here and here.

We acknowledge that it may seem as though an impostor sits on the ‘throne’ where the rightful heir should reside but as with all our cover art, we make cover decisions based primarily on artistic and visual impact rather than scientific accuracy. Our cover artist does a wonderful job creating or finding candidate images and we fell in love with this image as soon as we saw it and nothing she could do with the Drosophila melanogaster images we had on hand could match the weight and presence of the image. We felt anything else would fail to do justice to the weight of the content on the other side of the cover.

One reader kindly provided a photograph of Drosophila melanogaster that he took on a white background as an example of what could be done in a short amount of time and in five minutes of fun I mocked up a cover with it so our readers unfamiliar with Drosophila melanogaster can see what all the fuss is about.

No doubt there will continue to be occasions in the future when a scientific inaccuracy on the cover gives rise to comments from our readers and we welcome their comments even if we are unable to devote more resources to trying to ensure that covers are as scientifically accurate as they are aesthetically pleasing.

Our June issue will be published a week from now on May 28, and as always it will include the popular Research Highlights section where we write short news stories about interesting methods described in the recent literature. Of course we are not able to highlight every interesting methods paper we find, so here are some others you may want to check out. Stay tuned for the June issue to see what we picked to highlight in the journal!

The automation of science

Science 324, 85 – 89 (2009)

Ligand-directed tosyl chemistry for protein labeling in vivo

Nat. Chem. Biol. 5, 341 – 343 (2009)

Developmental programming of CpG island methylation profiles in the human genome

Nat. Struct. Mol. Biol. 16, 564 – 571 (2009)

Enzyme cascades activated on topologically programmed DNA scaffolds

Nat. Nanotechnol. 4, 249 – 254 (2009)

Evidence for antisense transcription associated with microRNA target mRNAs in Arabidopsis

PLoS Genet. 5, e1000457 (2009)

A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds

Nat. Biotechnol. 27, 369 – 377 (2009)

Two-dimensional IR spectroscopy and isotope labeling defines the pathway of amyloid formation with residue-specific resolution

PNAS 106, 6614-6619 (2009)

Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging

Nat. Neurosci. 12, 553 – 558 (2009)

High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues

Genome Res. published online 17 April 2009

Diversity-based, model-guided construction of synthetic gene networks with predicted functions

Nat. Biotechnol. 27, 465 – 471 (2009)

Single-molecule electrocatalysis by single-walled carbon nanotubes

Nano Lett. published online 14 April 2009

Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena

Nature 458, 1145 – 1149 (2009)

Fabricating genetically engineered high-power lithium ion batteries using multiple virus genes

Science 324, 1051 – 1055 (2009)