There was a funny comment by Friedemann Schrenk in a recent radio duo podcast [link to br online] that the human head sits with a wrong orientation on the human body as the pipelines for food and air cross over. Continue reading Human head with wrong orientation?
It sounds unbelievable – not only to me but also to the editors of Nature who needed half a year to publish a paper of (probably the first true) genetic treatment. Two high-throughput screens comprising ~800,000 low molecular weight compounds were needed to identify 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-benzoic acid Continue reading Ending decay (and suffering)
This now post no. 3 in a rather short time period about location of a behavioural trait to a certain brain region Continue reading Is utilitarian moral judgment hosted by the prefrontal cortex?
Here comes the reference to a first molecular system biology paper on asthma – something on my to-do list for 3 years. The authors constructed a biological interaction network using a database of curated molecular interactions. Continue reading Hubs and superhubs in asthma: low activity
A paper (that I found only recently) summarizes the responsibility of authorship in the life sciences. Sharing publication- related data is a key element of the life sciences and there is concern that in practice materials are not always readily available to the research community. U-P-S-I-D-E stands for “uniform principles for sharing integral data and materials expeditiously”. The authors come from major U.S. universities and companies and have developed 10 recommendations that should be in the curriculum of every PhD program – go to the executive summary at www.plantphysiol.org/cgi/doi/10.1104/pp.900068
Not all biobanks will need daily access to samples. Here comes a cost effect alternative – storage in permafrost regions. ZEIT magazine has an article about “Mine 3“, a former coal mine in the Arctic. Already the first 10,000 samples have been stored there at -3,5 degree Celsius. BBC and Wikipedia have also information about Svalbard Global Seed Vault Continue reading Low cost biobanking
1 MB is 1 Megabyte is 1,000,000 bytes and 1 Mb is 1 Megabase is 1,000,000 nucleotides. Although a new nature paper doesn’t make any fuss about it, there are 3,93 mutations / Mb in cancer tissues (in total they found 1,007 mutations by scanning 274 Mb from 210 cancer tissues). Continue reading 3,93 mutations / Mb
ATG16L1 is now confirmed as a candidate gene for Crohns disease:
Specifically, the LD structure and association mapping around the most associated SNP […] rs2241880 implicated a region on chromosome 2q37.1 containing a single gene known as ATG16 autophagy–related 16-like 1 (ATG16L1) […] Logistic regression analyses conditional on A197T in the family-based samples indicated that this coding variant can fully explain the association signal to this locus; thus, we consider this to be the causal risk variant.
Excellent to have this replication, although the argument above cannot convince me that this already a causal variant.
ATG16L1 seems to be most abundant in CD4+ and CD8+ cells and knockdown of the gene will lead to loss of S. typhimurium autophagy. Does rs2241880 really induce a loss of function and how does it relate to TLR7 and NOD2/CARD15 signalling?
The authors of another Nature paper believe that there is a primary NF-kB signalling defect in the Toll-like receptor activation by intestinal bacteria – see also KEGG pathways.
It will be much easier now to ask the right questions.
Already some time on my desk – a highly interesting pharmacogenomics approach published in issue 1 of PLoS 1. By comparing the muscle transcriptome with the plasma lipidome the authors tried to map a suspected pathway leading to statin-induced myopathy. Continue reading A new pharmacogenomic approach
A 3rd paper in nature genetics details the filaggrin gene structure: exon 3 has 10 repeats (as well as three variants FLG8+, FLG10+, FLF8+10+) and 15 SNPs – one of the few success stories in allergy research. In the discussion section, they ask the rhetoric question:
This study raises questions of interest to the complex trait field. Would SNP tagging of these multiple, relatively rare alleles, with frequencies no greater than 0.013, have readily identified this particularly strong susceptibility gene?
Nay, nay.
Waiting to exhale was a book in 1992 (“Right now I am supposed to be all geeked up”). Waiting to exhale then was a movie in 1995 (“Friends are the people who let you be yourself… and never let you forget it”). And finally Waiting to exhale was the title of a meeting report 1995 Continue reading Waiting to exhale
is another attempt to explain why replication fails frequently in genetic epidemiology. Zöllner and Pritchard write in the AJHG (their server is currently down)
For a variant that is genuinely—but weakly—associated with disease, there may be only low or moderate power to detect association. Hence, when there is a significant result, it may imply that the genotype counts of cases and controls are more different from each other than expected. Consequently, the estimates of effect size are biased upward. This effect, which is an example of the “winner’s curse” from economics depends strongly on the power of the initial test for association. If the power is high, most random draws from the distribution of genotype counts will result in a significant test for association; thus, the ascertainment effect is small. On the other hand, if the power is low, conditioning on a successful association scan will result in a big ascertainment effect.
I haven´t fully understood the following argumentation, but promise to revisit it some times later, yea, yea.
Curative medicine contributes only 10% to 40% to individual health (figures are depending on models and methodology according to a recent commentary in the Deutsche Ärzteblatt, for milestones check the BMJ) – a reason why I finally decided to become an epidemiologist. Continue reading Gary Taube’s limits and my interest in molecular epidemiology
Science has an interesting paper that relates to an earlier post here and a central question in immunology. How do T cells differentiate int both short-lived effector cells (that combat infections) and long-lived memory cells. Continue reading Divide and conquer
Science magazine today reports another ego trip.
A U.S. company [454] has begun to trickle out information on a unique DNA study it calls “Project Jim,†a crash effort to sequence the entire genome of a single individual. The results are likely to be made public this summer. Anonymity is out of the question: It has already been announced that the genome belongs to James D. Watson, winner of the Nobel Prize and co-discoverer of DNA’s structure. Watson won’t be alone: Harvard Medical School has approved a plan by computational geneticist George Church to sequence and make public the genomes of well-informed volunteers—including his own. And J. Craig Venter says his nonprofit institute will soon release a complete version of his genome.
My daily newsletter says that Roche is going to acquire 454 for $155M and plans to use the sequencer for IVD applications, I hope they will forget “Project Jim” somewhere on a harddisk.