Monkeyshines

Archive for January, 2011

“Running to the swings, running away from Satan…”

I don’t really understand why, but one of my hoomins (who I don’t see much of lately) is doing a lot of running. Perhaps she’s running away from a big rotten dog. Anyway, she seems to want other hoomins to pay her to do this running – maybe she’s a bit too loud for those of us with delicate ears, and people would be glad to pay her to be a bit further away. But it seems important, and I’m keen on anything that makes my hoomins happy, since that generally results in more treats for me; so please do be generous.

Present Tense Book Review – One Good Turn

One Good Turn is the follow-up to Case Histories, by Kate Atkinson. I like it better than that book so far; the characterisation is great, and there’s plenty of action, again delivered with a real sense of place (Edinburgh, rather than the former book’s Cambridge).

That is all, I have no grandiloquent insights to offer, I’m just enjoying the book.

Present Tense Book Review – Hand Me Down World: Part 3

(Part Two of this Present Tense Book Review.)

In the last third of the book we hear from Ines, the young African whose story has been unravelling through the testimony of others. It’s interesting to have multiple points of view in the narrative, but they’re a bit too far apart for my (admittedly ropey) memory. I’m sure there are all sorts of conflicts between the stories, and lots of thought-provoking nuances, but much of it went over my head, as I couldn’t remember the details of what had occurred previously. So either Ines comments on the inconsistencies (having read other people’s stories before writing her own), or I have to flick back if I get the sense that I’m missing something. I read a very good book last year that messed around with linguistic and narrative devices, and that had an index which was playfully incomplete as part of the messing around, but was also quite handy. Although I’m not really sure if that would have worked here.

I think this book would bear up well to a second or third reading, and unless you’ve got a particularly good memory, that is perhaps the only way to appreciate it properly. However, I didn’t enjoy it so much that I want to re-read it immediately. It’s unconvential, and fun, in an intellectual, noodly kind of way; but the narrative is a bit thin, and none of the characters endeared themselves to me. Which might have been the point, but it doesn’t exactly make the book a joy to read.

Present Tense Book Review – Hand Me Down World: Part 2

(Part One of this Present Tense Book Review.)

My initial concerns about the book remaining fragmented have mostly been allayed; the middle chunk of the book concentrates on a few central characters, and you can comfortably settle yourself behind their eyeballs. The literary device of the (partially) unreliable narrator comes to the fore here, with mostly subtle, but occasionally wildly different takes on the same events. The author rams this home with the fact that one of the characters is blind; an obvious trick when you want to make points about how we perceive, and are perceived by, others, but it works well nonetheless. The blindness feels like a natural part of the story, rather than being crowbarred in.

The plot hasn’t really moved along much lately, although enough happens to keep things ticking over, and my curiosity alive. This middle bit is much more about character than narrative, which is fine, but I’ll like the book better if it adds a bit of drama and action to the mix soon.

A cat who is almost as handsome and talented as me

Despite having me to stroke and lavish attention on, my hoomins are strangely interested in the noisy light-box in the corner of one of my rooms. I do not particularly like this distracing them, so I would like to emphasise that I am not the cat who is editing the new ‘Footloose’ film. He is a handsome devil, though, isn’t he.

CEB Journal Club: Andam et al. (2010)

Members of the Computational and Evolutionary Biology (CEB) group at the University of Manchester participate in a monthly journal club, where a paper of broad interest is discussed. Here, I briefly describe the paper and its context, and summarize our conclusions about the methodology and results presented. (I have attempted to represent the discussion and consensus of the group, but any inaccuracies are my own.) For your reading convenience, this post is available as a pdf pdf.

Biased gene transfer mimics patterns created through shared ancestry. Cheryl P. Andam, David Williams, and J. Peter Gogarten (2010) PNAS 107: 23, 10679-10684. PubMed: 20495090
(Presented by James Allen at Jabez Clegg, 28th July 2010)

The paper in a sentence: The authors describe a specific case of a gene that makes a bacterial enzyme, which has been horizontally transferred between species in a biased manner, such that the molecular evidence resembles that of a gene transferred by descent from parent to offspring.

Background: Until relatively recently, genetic information was thought largely to have been transferred from parent to offspring, analogous to a branching tree structure. The applicability of this analogy for all forms of life is under debate, however, given the discovery of the extent of other mechanisms for gene transfer in bacteria and other single-celled organisms. Horizontal gene transfer (HGT) refers to the process where genetic data from one organism is transferred to another which is not necessarily related, nor even necessarily the same species; the prevalence of HGT calls into question not only the ‘tree of life’ metaphor (suggesting, perhaps, that a network analogy is more appropriate), but also the (already rather labile) concept of species.

The paper in detail: The authors present one key result, which is supplemented by evidence from three other sources which would not be convincing in isolation, but here provide valuable circumstantial support. The results are based on a particular enzyme, which has the important property (for this analysis) that it has two distinct types. The main result is that the tree in figure 1 in the paper, generated by looking solely at this enzyme, has two distinct sub-trees, representing each of the the two types. Each one of these sub-trees closely resembles the tree that most likely characterizes the vertical inheritance of genetic data, i.e. the ‘species tree’ in figure 2. It is not easy to quantify whether one tree structure resembles another, particularly with the number of species used here; the authors look at the distances along the tree branches that separate all pairs of species, which discards information about some of the tree structure, but does not prevent them from convincingly demonstrating that the sub-trees for each type resemble the species tree. Moreover, in the species tree, the species with the same type of enzyme are grouped together within broader groupings at the phylum or class level; i.e. there are patches of red and green branches (representing the two types) in figure 2. This is evidence for biased HGT because it shows that HGT occurs not in a random fashion, but more often between more closely related species.

Another line of evidence presented is that a scenario of gene gain and loss that would explain the trees is far less likely than one where some degree of HGT occurs; the authors gloss over the fact that this demonstrates that HGT, rather than biased HGT, has most likely occurred. Additionally, the genes that surround the enzyme’s gene are found to be similar for both types, which would not be the case if the genes were being repeatedly gained and lost; again, this is evidence for HGT, not necessarily biased HGT.

The final piece of supporting evidence comes via simulations of biased and unbiased HGT, which result in data that resembles the real data. Some of the choices for the simulations are questionable, in particular the modelling of reciprocal transfer events, meaning that genes from two species are swapped. This does not reflect the biological reality, where the transfer generally happens in one direction only. Also, an extreme bias is modelled, using an exponential function, so that transfers are likely to occur between only the most closely related species – this may well be realistic, but the use of this particular model is not justified by the authors. Finally, the unbiased and biased transfers are simulated sequentially, which was perhaps done as it is often easier to show that something is changing, rather than staying the same, but is an uncommon approach that makes it difficult to interpret the results.

Journal club conclusion: While not wholly convinced by some of the evidence presented, particularly the approach to simulation, we believe that the main conclusions of the paper are valid: in the case of this particular enzyme, the horizontal gene transfer is biased, such that transfer is more likely between more similar species, and thus the molecular data provides the same signal as transmission through vertical inheritance. It remains to be shown how widespread this phenomenon is; if HGT generally reinforces, rather than contradicts, vertical inheritance of genetic material, then the tree of life analogy may well be useful for practical purposes, even if does not reflect the true evolutionary history.

Present Tense Book Review – Hand Me Down World

This is a book by Lloyd Jones, a Christmas present from Mrs. Monkeyshines, bought because Amazon recommended it after she bought me Nemesis, by Philip Roth for my birthday. I’m about a quarter of the way through, and it’s quite good rather than amazing.

In terms of subject matter, it reminds me of a book that I bought for my mum’s birthday, and which I subsequently read, because she really enjoyed it (the Monkeyshines clan do occasionally buy each other gifts which aren’t books, by the way). That book, The Other Hand, by Chris Cleave, was OK, but not particularly life-changing, as the rather pompous and prententious jacket blurb suggested. In that, the story of a young, female, African illegal immigrant in western europe was told in the first person; in Hand Me Down World there are multiple narrators, each given chapters of varying length, who relate their interactions with a young, female, African illegal immigrant in western europe. In this respect it is similar to another book I read last year, English Passengers, by Matthew Kneale. In that book, however, there were only a limited number of (recurring) narrators, and so it wasn’t too jarring when the viewpoint switched. In Hand Me Down World, most characters only have fleeting interactions with the African woman, so you find yourself jumping from one voice to the next. It’s certainly skilful writing, to be able to give each character a distinctive voice, but I will find it a bit wearing if this approach continues for the whole of the novel. It’s certainly an interesting approach for presenting a story, but I can imagine it feeling more disjointed as I read on.

T1DBase: type 1 diabetes, and my part in its downfall

Apropos of a new T1DBase publication (Burren et al. 2011) (in which I am kindly acknowledged), I thought I’d write a bit about some of the work I did there (Hulbert et al. 2007). I envisage this being the first of maybe three instalments, so before going into detail about the specific projects that I worked on, I’ll explain what T1DBase actually is, and why I’m proud to have worked on the project. For your reading convenience, this post is available as a pdf pdf.

T1DBase is a resource for the type 1 diabetes (T1D) research community, and it has strong ties to the JDRF/WT Diabetes and Inflammation Laboratory (DIL) in Cambridge, which is headed up by John Todd. (When I worked at the DIL we collaborated with the ISB and a group at UPenn, but this is no longer the case.) Type 1 diabetes is an auto-immune disease, that primarily manifests in childhood, so was formerly known as juvenile diabetes. The symptoms are similar to those of type 2 diabetes, but the aetiology is quite different (Todd 2010), and type 1 diabetes is genetically more similar to diseases like rheumatoid arthritis and coeliac disease (Smyth et al. 2008).

I worked on T1DBase for three years, from Jan 2006 to Dec 2008, which was a period of massive change in our understanding of the genetics of type 1 diabetes, primarily due to the emergence of genome-wide association studies (GWAS). The DIL was heavily involved in one of the first landmark studies (Todd et al. 2007; Wellcome Trust Case Control Consortium 2007), as part of the WTCCC (Wellcome Trust Case Control Consortium; don’t worry, I think that’s the last of the acronyms). Results from that and subsequent GWAS (e.g. Cooper et al. 2008; Barrett et al. 2009) generated a host of new T1D susceptibility regions, and a better (although still far-from-complete) appreciation of the genetics of this complex disease. (I’ve cited GWAS publications that I was involved in, or that were written by colleagues at the DIL, but T1DBase also gets data from a range of other sources; see the website for more information.)

The people behind T1DBase curate the GWAS results, and make them available as raw data and, more usefully, as region summaries that tie to analyses of genes and variants (i.e. SNPs), as well as cross-referencing with mouse and rat data. It sounds so simple when you write a sentence like that, but there are, of course, very many challenges involved, both in terms of making sense of a huge amount of biological data, and in working out how to effectively present the results. And that’s not to mention the day-to-day work of maintaining a website, and programming collaboratively and efficiently. I very much enjoyed working on the T1DBase project; I learnt loads, both about disease genetics and programming, and it was always a fun environment to work in (with regular tea breaks, too…) And it was nice to be in a job where, in some small way, I was able to constructively contribute to important and useful research into type 1 diabetes.

References

  • Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C et al. 2009. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics 41(6): 703-707. PubMed: 19430480
  • Burren OS, Adlem EC, Achuthan P, Christensen M, Coulson RMR, Todd JA. 2011. T1DBase: update 2011, organization and presentation of large-scale data sets for type 1 diabetes research. Nucleic Acids Research 39(Database issue): D997-D1001. PubMed: 20937630
  • Cooper JD, Smyth DJ, Smiles AM, Plagnol V, Walker NM, Allen JE, Downes K, Barrett JC, Healy BC, Mychaleckyj JC et al. 2008. Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nature Genetics 40(12): 1399-1401. PubMed: 18978792
  • Hulbert EM, Smink LJ, Adlem EC, Allen JE, Burdick DB, Burren OS, Cassen VM, Cavnor CC, Dolman GE, Flamez D et al. 2007. T1DBase: integration and presentation of complex data for type 1 diabetes research. Nucleic Acids Research 35(Database issue): D742-746. PubMed: 17169983
  • Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JHM, Howson JMM, Stevens H, McManus R, Wijmenga C et al. 2008. Shared and distinct genetic variants in type 1 diabetes and celiac disease. The New England Journal of Medicine 359(26): 2767-2777. PubMed: 19073967
  • Todd JA. 2010. Etiology of type 1 diabetes. Immunity 32(4): 457-467. PubMed: 20412756
  • Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, Bailey R, Nejentsev S, Field SF, Payne F et al. 2007. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nature Genetics 39(7): 857-864. PubMed: 17554260
  • Wellcome Trust Case Control Consortium. 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145): 661-678. PubMed: 17554300

Past Tense Book Review – The Girl with the Dragon Tattoo

Again I have failed to write a present tense book review, although this time it’s more because I didn’t really have anything to say until I got to the end (although my slothfulness played a part too). If you’re not already aware of this book, then you probably won’t be interested in it. If you like intelligent thrillers, then this is a good example of the genre, with interesting characters.

For all the complicated, deep characters, a book like this lives or dies on the plot, which is intricate and largely involving, although there are two holes that you could drive a Volvo through. Spoiler alert: click to reveal spoiling plot holes. But despite these cavils, it’s a fun journey, and I shall be tackling the second book of the trilogy anon.

Oh, and one final thing, all of the acronyms in the book were full-stopped, e.g. C.D. and P.C. rather than CD and PC, which grates on the eyes after a while.

Past Tense Book Review – Nemesis

This was going to be one of my incredibly popular (i.e. read by Mrs. Monkeyshines and/or Binky) present tense book reviews, but a) I’ve been too busy doing nothing over Christmas to faff around on my website, and 2) it’s quite short, and also superb, so I rattled through it in no time. It’s by Philip Roth, by the way.

I’ve liked some of his earlier books very much, and Nemesis is brilliant. I’ve written and deleted several attempts at explaining why, but it’s hard without sounding facile; just trust me, it’s much better than I make it sound. It’s framed fabulously, with a narrator relating one man’s personal crisis during a polio outbreak in Newark in the 40s, almost 30 years later. The panic and the grief caused by the mysterious, virulent polio virus are brutally and movingly described. But the story is mostly about one man, Bucky Cantor, a decent, if rather humourless, young man, whose life is ruined by polio. Or, perhaps, a man who lets his life slip through his fingers.

Roth paints a complex, nuanced portrait of a man, and dissects the effects of chance and contingency on an individual’s life, and does so with wonderful, masterly style. A thoughtful, enjoyable read.