RNA binding proteins and their recognition elements within the transcriptome
The issue will focus on RNA binding proteins (RBPs), and the RNA molecules and motifs to which they bind: it is this RNA landscape, sculpted by RBPs, that we believe to be a particularly exciting and fast-moving area of research at the present time.

Read more]]> Genome Biology is very pleased to announce the Guest Editors of our special issue on the RBPome as John Rinn and Jernej Ule. The issue will be published in late 2013.

RNA binding proteins and their recognition elements within the transcriptome
The issue will focus on RNA binding proteins (RBPs), and the RNA molecules and motifs to which they bind: it is this RNA landscape, sculpted by RBPs, that we believe to be a particularly exciting and fast-moving area of research at the present time.

John Rinn

Jernej Ule

Acta Neuropathologica Communications (ANC), a new open access journal focusing on the pathology and mechanisms of neurological disease has launched today with  BioMed Central. Led by Editor-in-Chief Werner Paulus, a Professor of Neuropathology at University Hospital Münster, the journal hopes to emulate the success of its older, sister journal, Acta Neuropathalogica published by Springer.

Like Acta Neuropathalogica, ANC will publish high quality research and aims to get a decision on manuscripts to authors within 11 days, however it differs in the fact that it will only publish manuscripts which require no or only minor revisions. Werner Paulus explains the rational for this policy in his launch Editorial  “One of the chief complaints from ...

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Acta Neuropathologica Communications (ANC), a new open access journal focusing on the pathology and mechanisms of neurological disease has launched today with  BioMed Central. Led by Editor-in-Chief Werner Paulus, a Professor of Neuropathology at University Hospital Münster, the journal hopes to emulate the success of its older, sister journal, Acta Neuropathalogica published by Springer.

Like Acta Neuropathalogica, ANC will publish high quality research and aims to get a decision on manuscripts to authors within 11 days, however it differs in the fact that it will only publish manuscripts which require no or only minor revisions. Werner Paulus explains the rational for this policy in his launch Editorial  “One of the chief complaints from authors is when referees suggest major revisions that may or may not be useful. As an author and an editor I sometimes wonder whether these often unnecessary additional experiments, which can take many months, are worth the effort.  For manuscripts submitted to ANC we request only minor revisions that can be performed (and have to be performed) within three weeks… Submissions that require major revisions to be deemed scientifically sound will be rejected.”

This policy, along with an Editorial  Board of carefully selected and experienced members who support Werner with peer review, mean that an article should take no longer than two months from submission to publication in ANC. Why not give it a try and submit an article today?

Visit the journal website to read all the launch articles, including the insightful review by Lang et al. in which they discuss the challenges of the Braak Hypothesis, suggesting how Prion-like processes may mediate the pathology progression.

To keep abreast of all new publications you can sign up for article alerts from ANC here. For more information, please visit the journal website or contact the Editorial Office.

Progress has been made in early detection and treatment of breast cancer but little is understood about how women can reduce their risk of developing the disease. Child-bearing is one factor identified to reduce this risk. If a full-term pregnancy occurs before the age of 20, the risk of developing breast cancer is halved. Yet the mechanism through which this works remains unexplained.

A new publication  in Breast Cancer Research uses a novel approach to answer this ...

Read more]]> Breast cancer is the most common cancer in the United Kingdom and constitutes the leading cause of cancer-related death in women worldwide. One in eight women can expect to develop breast cancer at some point in their lifetime.

Progress has been made in early detection and treatment of breast cancer but little is understood about how women can reduce their risk of developing the disease. Child-bearing is one factor identified to reduce this risk. If a full-term pregnancy occurs before the age of 20, the risk of developing breast cancer is halved. Yet the mechanism through which this works remains unexplained.

A new publication  in Breast Cancer Research uses a novel approach to answer this question. The authors, including Editorial Board Member Professor Mohamed Bentires-Alj, use transcriptome analysis, immunohistochemistry, colony formation assay, and mammary fat pad transplantation to look at the effect of early parity (pregnancy) in mice on distinct subpopulations of mammary epithelial cells. This differs from past studies, which have instead looked at the mammary gland as a whole.

The authors found that parous mice had an upregulation of differentiation genes, a decrease in the Wnt/Notch signalling ratio (a potentially carcinogenic pathway which controls cell proliferation and differentiation), and a reduction of proliferation specifically in basal stem/progenitor cells.

These results support the theory that early pregnancy changes gene expression in specific mammary gland cells to promote differentiation, reduce proliferation and ultimately protect against breast cancer. This exciting new study opens the door to future research into inhibition of the Wnt pathway and the possibility of drugs which may be able to mimic parity-induced protection against breast cancer.

Eleanor Tyler
Editorial Assistant – Breast Cancer Research

Now, recombination hotspots are a bit of an enigma themselves: for a long time no one could put their finger on how these hotspots are defined – or chosen. But, as it ...

Read more]]> Taking into account the importance of the role that genetic recombination plays in evolution, adaptation, survival, and – perhaps most importantly – sex, we know surprisingly little about the molecular foundations of this phenomenon. What we do know is that genetic recombination is not a completely random process; that it follows a pattern. Some chromosomal regions are more, and some less, likely to be affected by double-stranded breaks – and the recombination events that follow. Areas with a high frequency of recombination have been appropriately dubbed ‘recombination hotspots’.

Now, recombination hotspots are a bit of an enigma themselves: for a long time no one could put their finger on how these hotspots are defined – or chosen. But, as it happens, something else’s fingers are involved: those of the zinc finger protein PRDM9. The mystery slowly started to unveil in 2010 when three articles in Science identified PRDM9 as a key player in the process of recombination hotspot determination.

DNA being repaired after recombination

Thanks to those papers and subsequent work, we know that PRDM9 binds to specific DNA sequences, activating chromatin and guiding the generation of double-stranded breakpoints. But there is still some confusion regarding the make-up of these DNA sequences, and this is the problem that Petkov and colleagues address in an article published in Genome Biology last week.

In the article, Petkov and colleagues take two variants of mouse PRDM9, express them in E. coli and then assess which sequences in four known hotspots the protein binds to, and how. As it turns out, for the same variant of PRDM9 there is very little sequence similarity between the different binding sites, and the specificity of each of the protein’s dozen zinc fingers seems to be context-dependent. As part of this survey, the authors also identify the shortest DNA sequence required to bind PRDM9.

The data collected by Petkov and colleagues represents one of the most detailed and comprehensive PRDM9 DNA-binding maps described to date. Their work, however, raises more questions than it answers: instead of one consensus sequence, the article identifies a whole collection; instead of defining a set of rules for PRDM9 interactions with DNA, Petkov and colleagues suggest that its zinc fingers are quite fickle in this regard. And this is all already apparent in an in vitro study – PRDM9 behavior may be revealed as even more complex when we move to in vivo studies of this capricious protein, and to human-dedicated models.

Life's secret
For this reason, when I look at one of the beautiful X-ray diffraction photos taken by Rosalind Franklin and her PhD student Ray Gosling in the early 1950s, from painstaking work performed on calf thymus samples in gloomy ...

Read more]]> One of the most wonderful things about science, to my mind, is the way its fundamental principles are simultaneously both universal and personal. Quantum physics helps to explain the nature of grandiose concepts such as time and space, but it also applies to the insignificant particles that make up my own cells. Equally, within these very cells, at any moment, biological processes newly reported in the literature are taking place, as are those that have yet to be discovered.

Diamond in the rough: an early X-ray diffraction image of crystalline DNA

Life's secret
For this reason, when I look at one of the beautiful X-ray diffraction photos taken by Rosalind Franklin and her PhD student Ray Gosling in the early 1950s, from painstaking work performed on calf thymus samples in gloomy basements by the banks of the River Thames, I know that my own DNA could produce just such an image: the stark, spotty diamond patterns that told the secret of the double helix – and, with it, the secret of life itself.

Today is DNA60, the 60th anniversary of the three seminal Nature papers that first described DNA's double helical nature. Watson and Crick's paper – the best known of the three – presented the double helix model of DNA’s structure, astounding in its simplicity and elegance. Most of all, the paper was shocking because the structure itself revealed the mode of genetic replication, and in doing so proved beyond doubt that DNA was the stuff of genes, the chemical of genetic inheritance. Nature is rarely so kind in its revelations, and seldom so memorable.

Rosalind Franklin, Ray Gosling and the King's version of the double helix story
Also remarkable in Watson and Crick's paper was the total absence of experimental data; instead, they had used X-ray diffraction data generated by Franklin and Gosling as the basis for their model. These data were published in an accompanying paper, and so acquired parity of sorts in the literature, but Watson and Crick had very much won the race to the double helix.

It's often said that, well – to the victor the spoils! And so it was with DNA: Watson wrote a book that become the best known account of the double helix's discovery. Many years later, however, a different perspective, by Rosalind Franklin's biographer, attracted some attention and, as a result, more emphasis is now placed on the role of Franklin and her colleagues at King's College London.

Ray Gosling

On this, the 60th anniversary, Genome Biology publishes yet another account of the story, that of Ray Gosling, Franklin's PhD student. Gosling describes how he was the first person to crystallize DNA, before Franklin was even involved in the project. What had been fuzzy patterns were suddenly dazzling diamonds, and it's an image that leaves Gosling in awe to this day.

Over at Biome, you can listen to an audio excerpt of our interview with Gosling, in which he describes – with some amusement – a trip made by the King's DNA team to Cambridge, where they viewed Watson and Crick's lesser known first model. As Franklin was very quick to point out, this beginner's attempt contained a number of major errors.

DNA: past, present and future
As a further celebration of DNA60, we canvassed our Editorial Board members for their most memorable moments in the field of genome biology since the double helix. The clear emergence of introns as a favorite discovery will no doubt be pleasing to those nostalgic for the pre-omics days of classical biology, and you can read a free excerpt of this section of the article at Biome.

Outside of introns, selections included the human and mouse genome projects and sequencing technologies. Recent improvements in the sensitivity of the latter of these has of course brought about the era of the data deluge and a high demand for bioinformaticians. So how better to round off our honoring of DNA Day than with a 5-step DNA60IFX Bioinformatics Challenge?

Update: The winners of our DNA60IFX Bioinformatics Challenge were announced at 8 pm Eagle Time, DNA Day. Although the challenge has now concluded, we've left the puzzles open for anyone who would like to try them out for fun. For more info, please see the Challenge homepage.

See also: We reviewed the Wellcome Trust's special DNA60 conference, 'Genomic Disorders 2013: From 60 years of DNA to human genomes in the clinic', here.

Read more]]> This year's Abcam conference on 'non-coding RNAs, epigenetics and transgenerational inheritance' had a distinct Lamarckian flavor with conference Chair and 2013 Hooke medal recipient, Eric Miska, recommending Arthur Koestler's 'The case of the midwife toad' as extracurricular reading. In addition to his literary recommendations Miska discussed his recently published observations on the ability of piRNA phenotypes to be inherited through generations in C. elegans. The nematode and RNAi theme was continued in Scott Kennedy's talk, which focused on his recently published work on identifying genes required for RNAi inheritance in C. elegans. He identified such genes through screening for mutants defective in transmitting RNAi phenotypes to the next generation, but which are still able to perform RNAi themselves. This has led to the identification of the nuclear argonaute protein HRDE-1, which directs silencing in germlines. Interestingly, hdre-1 deficient worms exhibit mortal germlines, which through successive generations ultimately leads to sterility.

Peter Sarkies, a Post-doc in the Miska lab, shared his exciting work on understanding the function of the RNAi pathway in nematodes, which clearly hasn't arisen purely for the benefit of molecular biologists. Oded Rechavi continued this theme with a discussion on the function of trangenerational RNAi. His work, published in Cell 2011, has identified the trangenerational inheritance of virus-derived siRNAs, suggesting that this mechanism may be involved in providing protection to offspring. However, to date only one C. elegans-infecting virus has been identified.

Transgenerational epigenetic inheritance was examined not only in nematodes but also in mouse models, including a presentation of ongoing work by Erica Watson on the analysis of transgenerational epigenetic effects due to abnormal folate metabolism using a mouse model deficient in a key folate metabolism enzyme. Anne Ferguson-Smith discussed recent work that follows on from previous publications on a mouse model of intergenerational epigenetic inheritance. This model is concerned with the effects of severe maternal caloric restriction, which leads to low birth weight offspring – a characteristic that is known to be associated with increased risk of obesity, diabetes and cardiovascular disease later in adult life. This effect is transmitted over at least two generations and her talk focused on understanding the underlying epigenetic modifications responsible for this phenotype.

Investigation of transgenerational epigenetic inheritance in plants was also discussed, including a delightful presentation by Genome Biology Editorial Board Member David Baulcombe on generating transgenic plants. As previously shown by Baulcombe, sRNAs can move through the plant to distant locations, including across the grafted region of two plants. Baulcombe's recent work has shown that this phenomena can be exploited in order to generate (epi)genetically modified plants.

While transgenerational inheritance and small RNAs appeared to dominate the talks, long non-coding RNAs were not forgotten with a truly absorbing talk by Genome Biology Editorial Board Member John Rinn on his recent work into understanding the functional of individual lncRNAs.

This two-day conference highlighted some of the major areas of investigation in this relatively young field, in particular the observance that acquired traits, mediated through epigenetic effects, can be passed onto offspring in a rather Lamarckian fashion.

Last Friday marked the first anniversary of the launch of Agriculture & Food Security. To celebrate this important milestone in the journal’s history, an anniversary editorial has been published, describing the achievements of the last year, and reiterating the importance of research on this significant global issue.  

Following a highly successful launch event at BioVision Alexandria – of which a highlights video is now available online – Agriculture & Food Security has had a rewarding first year of publishing. Over the last year, a number of highly accessed articles by eminent scientists in the field have been published. Topping this list is Albert Sasson’s review on tackling the food insecurity crisis ...

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Last Friday marked the first anniversary of the launch of Agriculture & Food Security. To celebrate this important milestone in the journal’s history, an anniversary editorial has been published, describing the achievements of the last year, and reiterating the importance of research on this significant global issue.  

Following a highly successful launch event at BioVision Alexandria – of which a highlights video is now available online – Agriculture & Food Security has had a rewarding first year of publishing. Over the last year, a number of highly accessed articles by eminent scientists in the field have been published. Topping this list is Albert Sasson’s review on tackling the food insecurity crisis in Africa, which has had over 11,500 accesses since publication in April 2012. The next article, Beddington et al.’s article on the role of scientists in tackling food security and climate change has had over 11,100 accesses since publication in July 2012.

In addition to the high quality articles published in the journal to date, a supplement on the important topic of the establishment of agricultural biotechnology partnerships in Africa was published in November. This supplement was guest edited by Calestous Juma, and devised by the Sandra Rotman Centre.

Most recently, a new thematic series on ‘Climate Smart Agriculture’ has been completed, with an editorial from guest editor Ademola Braimoh of the World Bank. This series comprises several thought provoking articles following from the ‘Global Science Conference on Climate –Smart Agriculture’. More information regarding this series can be found in an earlier blog post.

Lead by the Editors-in-Chief, Malcolm Elliott, Molly Jahn and Magdy Madkour, Agriculture & Food Security has made excellent progress so far, and is well on its way to becoming the leading resource for researchers and policy makers with an interest in alleviating global food insecurity. Manuscripts can be submitted via the online submission system, and to keep up to date with the journal’s progress sign up for article alerts, or for more information contact the editorial office.

Recently, we excited informatics enthusiasts with the prospect of a special Genome Biology Bioinformatics Challenge in honor of DNA60, but we were lamentably low on the detail. Here, we are putting that right.

So what is this Challenge all about then?
DNA60 celebrates the sixtieth anniversary of the publication of Watson and Crick's Double Helix, and Genome Biology will be marking the occasion, April 25th, with some special content. But we also wanted to have some fun, and to give away some prizes, so we decided to ...

Read more]]> Stand by for an important update on Genome Biology's highly anticipated, ultra-tricky, ultra-cool, *supreme* DNA60 Bioinformatics Challenge with a truly amazing prize…

Recently, we excited informatics enthusiasts with the prospect of a special Genome Biology Bioinformatics Challenge in honor of DNA60, but we were lamentably low on the detail. Here, we are putting that right.

So what is this Challenge all about then?
DNA60 celebrates the sixtieth anniversary of the publication of Watson and Crick's Double Helix, and Genome Biology will be marking the occasion, April 25th, with some special content. But we also wanted to have some fun, and to give away some prizes, so we decided to augment our coverage in the journal with a special Bioinformatics Challenge (we usually run these at our Beyond The Genome conferences).

The challenge will comprise five steps, and will begin 7 am ET on Monday April 22nd. The final step will be on DNA Day itself, Thursday April 25th.

Mike Schatz (l); James Taylor (r)

The prizes
Winner – the first correct answer receives a brand new, shimmeringly shiny iPad

2x runners-up - your choice of either free registration to Beyond The Genome or one-year subscription to Genome Biology

The plan
Each step of the Challenge will require you to use all the bioinformatics wherewithal that you can muster in order to identify a hidden sequence within a dataset.

Keep an eye on this blog and Twitter (@GenomeBiology and #DNA60IFX) for a link to the Challenge start-page. For subsequent steps, your previous answer will be the key to the URL with the instructions for the next step.

Questions and queries
If you have found this blog post to be irritating and/or confusing, then you can get in touch with the questions you want answered in the comments below, or through Twitter (@GenomeBiology or #DNA60IFX)

Update: The Challenge is now live. The homepage has full details, including a schedule of the steps. Good luck!

So it was not entirely out of keeping with expectations when philosopher (and former candidate for Slovene of the year) Renata Salecl stepped onto the podium and asked:

'Should I kill myself, or have ...

Read more]]> It is not unusual per se for Nobel laureates to be quoted at genomics conferences, but it is perhaps a little out of the ordinary when the Nobel Prize in question is for Literature. But, then again, the Wellcome Trust's 'Genomic Disorders 2013: From 60 years of DNA to human genomes in the clinic' was not your run-of-the-mill conference; instead, a mesh of current research and historical (and futuristic) perspective paid tribute to the 60th anniversary of Watson and Crick's discovery of the double helix.

So it was not entirely out of keeping with expectations when philosopher (and former candidate for Slovene of the year) Renata Salecl stepped onto the podium and asked:

'Should I kill myself, or have a cup of coffee?'

For those unfamiliar with mid-20th Century Absurdist literature, these are the (translated) words of French-Algerian faux existentialist Albert Camus, taken from the pages of his 1942 novel L'Étranger. Salecl chose the quote as an illustration of the anxiety surrounding ambiguous data generated by modern genetic techniques. Camus' protagonist, Meursault, bumbled through life making choices where the options were clear-cut: with genetic data, we are faced with unknowns, risk factors and grey areas.

Absurd genomics
Meursault ultimately ended up on death row after committing murder, so maybe we should not let him inform the debate too strongly. Salecl reminded us, however, that a real problem of unwarranted certainty exists when handling forensic genetic data in legal cases. And such miscalculations may also result in death row, but for innocent victims of judicial inadequacies.

Salecl offered examples of incompetence and compromised integrity on the part of forensic scientists, and even suggested that a malevolent individual, in the mold of Harold Shipman, might deliberately falsify forensic reports as a form of sadistic power trip. Suffice it to say that the prospect of incompetence is worrisome enough, especially when one considers the number of forensic scientists who put their name to a recently published paper purporting to report the 'Bigfoot' genome sequence.

Genomes2people – but which bits and which people?
A more practical assessment of genetic uncertainty was put forward by Robert Green, of Genomes2People. Together with colleagues, Green has developed a set of recommendations for the reporting of incidental findings in genomic data, one of the main headaches of the personal genomes era that is opening up before us. He discussed studies into how people respond to such findings, and the general trend is an encouraging one: more exercise, more insurance take-up, and so on. Of concern, however, was the large number of people who are unable to accurately describe the risk factor reported to them, even when they can remember the details of what was said.

When experts were canvassed as to which type of incidental finding should be reported, taking into account disease type and the known risk of the variant, very little by way of consensus emerged. Perhaps there really is no right or wrong answer, but this is not an issue with room for neutrality – each finding is either reported or it isn't, and either way you are taking a point of view. Green and his colleagues have at least managed to arrive at a minimal list – encompassing 57 genes in 24 conditions – of risk variants that they recommend should be reported as incidental findings. But they also suggest each clinician should apply personal judgement to individual cases.

Variant-based therapeutics
Green made the point that incidental findings in genetics data seem to be held to a different standard to those derived from imaging data or physical examinations. Perhaps this is because many genetic findings are today not actionable. By conventional approaches (find a druggable target, and then a safe and specific drug for the target), patients have little hope of a successful remedy in the near future.

But Tamar Grossman, of ISIS pharmaceuticals, explained how therapeutic antisense oligos (ASOs) offer a whole new paradigm for rational drug design. One of the exciting features of ASOs is that they not only avoid the need to discover a druggable site (and then a small molecule of high affinity and specificity), but can also target the large number of genes for which no readily druggable site is discoverable.

ASOs can operate by a number of mechanisms, one of which is masking aberrant splice sites, as shown by Jennifer Lentz (Louisiana State University). In a recently published study, Lentz applied ASOs to a mouse model of Acadian-type Usher syndrome, which involves a specific mutation that promotes an inappropriate splicing event.

Lentz is able to prevent onset of the deafness and vestibular symptoms of Usher syndrome mice, although has not yet established whether this is also true of the blindness phenotype. Interestingly, Usher syndrome patients have expressed interest in translating these ASOs to the clinic, but only if it means prevention of blindness. Deafness, on the other hand, is viewed as natural variation – not a 'condition' that clinicians should seek to correct in utero.

DNA60
Rounding off the meeting with ASOs was fitting, given that they function through complementary base-pairing – the heart of Watson and Crick's double helix discovery, sixty years earlier, in the very same Cambridge streets now playing host to the conference in its honor. The progress made in genetics during these sixty years is really something to behold, and was fully on show at the meeting.

On the anniversary itself, 25th April, Genome Biology will publish some special content celebrating sixty years of the double helix, so please do look out for that. We are also hosting a special commemorative bioinformatics challenge, beginning a few days earlier and culminating on DNA day, of which you can read more here.

Global warming represents one of the greatest threats to society worldwide. The dual burden of climate change coupled with exponentially increasing populations means that our agricultural systems are under increasing pressure to produce food in unstable environmental conditions. The struggle to reach required productivity means that food security is fast becoming a significant threat to lives worldwide. Furthermore, in recent years it has become clear that not only is agricultural productivity threatened by climate change, current agricultural practices may in fact be accelerating atmospheric changes; agriculture is the leading cause of methane and nitrous oxide emissions, as well as a significant cause of deforestation and ...

Read more]]> Agriculture & Food Security publishes a new thematic series on ‘Climate Smart Agriculture’.

Global warming represents one of the greatest threats to society worldwide. The dual burden of climate change coupled with exponentially increasing populations means that our agricultural systems are under increasing pressure to produce food in unstable environmental conditions. The struggle to reach required productivity means that food security is fast becoming a significant threat to lives worldwide. Furthermore, in recent years it has become clear that not only is agricultural productivity threatened by climate change, current agricultural practices may in fact be accelerating atmospheric changes; agriculture is the leading cause of methane and nitrous oxide emissions, as well as a significant cause of deforestation and carbon emissions.

This new series has been published with the aims of highlighting the importance of developing policies which are climate aware for tackling food insecurity. The series follows on from a highly successful ‘Global Science Conference on Climate Smart Agriculture’ investigating the need for an emphasis on climate smart agriculture, whereby practices are better able to balance natural resource use and food production. The final article in the series, an editorial by Ademola Braimoh, who has guest edited the series has been published today. As a Senior Natural Resources Manager at the World Bank, Braimoh stresses the need for ‘science-policy integration for climate-smart agriculture’.

Articles included in the series include Sir John Beddington et al’s highly accessed article discussing the role of researchers in informing policy makers of measures to use resources more efficiently and adapt agricultural practices to climate change. Further articles cover landscape approach measures, ecosystem approaches and the role of smart crop varieties in food security.