Open dictionary with command-control-d in Mac OS X

In a recent MacMost Newsletter, I came across the following handy trick in Mac OS X: while the cursor is over a word (not necessarily selected), one can press command-control-d to open dictionary which pops up a little window with the word's definition. This works in Safari and Mail, but not in Preview (unfortunately).

Previously, when I need to check the definition of a word, I right-click on it and then follow the link "Look Up in Dictionary". This will launch or pop up Dictionary with detailed information about the word (Dictionary/Thesaurus/wikipedia).

The right-click method seems to integrate better with other Mac OS X applications. For example, it works with Preview as well. However, now that I know it, I sometimes prefer the command-control-d approach better; it is quick and non-obstructive.

IUPAC nucleotide symbols and their complements

Recently, I was interested in knowing the complements of all the IUPAC nucleotide symbols. As blogged previously, I am quite familiar with the "meaning of nucleotide IUPAC codes" (namely A/C/G/T, and R/Y/N etc). However, when I first check the Gene Infinity website on nucleotide symbols, it still puzzled me for awhile to figure out the meaning of the DNA alphabet (with complements), as except below:

A  C  G  T    M  R  W  S  Y  K    B  D  H  V    N
|  |  |  |    |  |  |  |  |  |    |  |  |  |    |
T  G  C  A    K  Y  W  S  R  M    V  H  D  B    N

For example, some degenerated IUPAC symbols are complemented to themselves (e.g., W–W and S–S), while others are seemingly "hard" to apprehend (e.g., B–V and D–H).

After thinking it for a bit, things begin to become clear. They are based on the complementarity of Watson-Crick base-pairs (A–T and G–C) and the meaning of each degenerated IUPAC nucleotide symbol. For example,

• W represents A/T, meaning weak (with only two hydrogen-bonds). The complements of A/T are T/A respectively, which is W again.
• B (not A) represents C/G/T, and their complements are G/C/A respectively, which is V (not U/T).

It is easy to verify that all other complementary pairs follow exactly the same basic principle.

Extract images from PDF files using 'pdfimages'

Once in a while, I need to extract an image (or a portion thereof) from a PDF file. Usually, I open the PDF file using 'preview' or Adobe 'Acrobat Reader', and take a screenshot which is then cropped to the desired slice. This manual method "works", albeit a bit tedious.

Recently, I came across the handy command-line utility program 'pdfimages' which allows for automatic extraction of all images from a PDF file. The basic usage is simply:

pdfimages   yourfile.pdf   prefix

This will extract all images contained in yourfile.pdf to files prefix-001.ppm, prefix-002.ppm etc. With option "-j", images in DCT format are saved as JPEG files.

Nice blog on English writing by Lynn Gaertner-Johnston

A while back, I was somehow curious to figure out the differences between entitled vs. titled. A colleague referred me to a blog post on this topic by Lynn Gaertner-Johnston. After reading the post, it became clear that over the years I had made the same mistake numerous times. I then corrected nearly all occurrences of "entitled" to "titled" in my blog and 3DNA forum posts. Ever since, I have been following Lynn Gaertner-Johnston's blog, titled "Business Writing", on a regular basis, and found it helpful to improve my English writing skills.

Under-citation of method papers?

Recently in the CCP4BB, there is an interesting thread with extensive discussions on "Citations in supplementary material". The original poster refers to the recent Acta Cryst D editorial with the same title in which the authors highlights the issue of under-citation to papers published in the International Union of Crystallography (IUCr) journals.

The main point is that method papers are more likely to be cited in the supplementary materials only, which are not indexed by PubMed, Scopus, Web of Science or Google Scholar etc. As a result, they are statistically undercounted, and "Journals and scientists that focus on publishing methodologically oriented papers are particularly affected." Specifically, through a survey of articles on protein or nucleic acid structure determination published in Cell, Nature, Science, and PNAS in 2009, the authors found that "almost half of all references to publications in IUCr journals end up being published in the supplementary material only."

The findings of the editorial resonate with my observations, and I cannot agree more with the authors that "in the end, methods need to be continuously developed and refined in order to ensure progress."

On the other end of the spectrum, some highly influential method papers are heavily cited. As an extreme case, the large number of citations to the 2008 paper "A short history of SHELX" by George Sheldrick helps rocket up the impact factor of Acta Crystallographica A by 20-fold to 49.9 this year!

Belorussian translation of 3DNA webpages

Recently, I communicated with Paul Bukhovko on the translation of 3DNA webpages http://rutchem.rutgers.edu/~xiangjun/3DNA/ into Belorussian. As the author of the original website, referred to as http://rutchem.rutgers.edu/~olson/3DNA/ (which is simply a soft link to the above URL) in the 2003 3DNA NAR paper, I was very surprisingly pleased when Paul asked for permission to perform the translation, which I gladly granted.

Regarding the process, Paul commented:

Was a pleasure to translate this page! It's kinda fresh and related to my professional interests, so I thought - why not, if the author allows to do so.

The translated page is at URL: http://www.movavi.com/opensource/3DNA-be. Interestingly, when I used Google Translate to convert the Belorussian version back to English, the outcome is pretty readable. In contrast, when the original English version is directly translated to Chinese, the result is beyond recognition!

Proper labeling of O1P and O2P atoms in a phosphate group

Recently, a question on the 3DNA o1p_o2p utility program in the forum led me to reflect on the proper labeling of O1P/O2P atoms in a phosphate group. As is well-known, in DNA/RNA structures, the phosphate group (see figure below left) connected two neighboring nucleosides.

The two nonbridging oxygen atoms of the phosphate group (the horizontal Os in the O-P=O line, left) are named O1P and O2P in PDB files (see also figure to the right). Stereochemically, O1P and O2P are also designated as pro-R and pro-S oxygens, respectively.

Presumably, the structural files in the PDB and NDB databases should be consistent and follow the standard nomenclature. In practice, however, some entries in the NDB had mislabeled O1P/O2P atoms (e.g., adh026). I first noticed this issue when I superposed the A-DNA adh026 to its 3DNA rebuilt version with the sugar-phosphate backbone. I observed an unreasonably large RMSD only for the octamer adh026, while the RMSDs were much smaller (as expected) for the B-DNA dodecamer bdl084 and the 146-bp nucleosomal DNA in pd0001 (see $X3DNA/examples/analyze_rebuild distributed with 3DNA v2.0). Since the standard building blocks in 3DNA were applied consistently, I traced the cause of the large RMSD problem to the PDB file of adh026 itself, and finally identified it was actually due to the mislabeling of the O1P/O2P atoms.

The utility program o1p_o2p was written specifically for the purpose of checking if the O1P/O2P atoms are properly labeled in a PDB file. In a phosphate group, if O1P/O2P are correctly labeled, then following O1P-->O2P-->O5' in a right-handed sense would point the thumb in the direction of O3' (see the figure up right). As always, how it actually works is best illustrated with an example. Shown below, the second phosphate in adh026 is used (as distributed with 3DNA), with GNU octave script. Here the O1P/O2P atoms are mislabeled since direction has a negative value. In contrast, for a properly labeled phosphate group, direction should be positive.

#ATOM      6  O3*   G A   1       8.396  -3.995  -1.948  1.00 30.86           O  
#ATOM     20  P     G A   2       8.163  -3.069  -0.619  1.00 32.38           P  
#ATOM     21  O1P   G A   2       7.401  -1.917  -1.218  1.00 32.09           O  
#ATOM     22  O2P   G A   2       7.280  -3.934   0.195  1.00 34.05           O  
#ATOM     23  O5*   G A   2       9.600  -2.800  -0.121  1.00 29.41           O  

P   = [8.163  -3.069  -0.619]
O1P = [7.401  -1.917  -1.218]
O2P = [7.280  -3.934   0.195]
O3  = [8.396  -3.995  -1.948]
O5  = [9.600  -2.800  -0.121]

O1P_to_O2P = O2P - O1P                    # -0.12100  -2.01700   1.41300
O2P_to_O5 = O5 - O2P                      #  2.32000   1.13400  -0.31600
O1P_O2P_O5 = cross(O1P_to_O2P, O2P_to_O5) # -0.96497   3.23992   4.54223
P_to_O3 = O3 - P                          #  0.23300  -0.92600  -1.32900

direction = dot(O1P_O2P_O5, P_to_O3)    # -9.2616 < 0: O1P/O2P mislabeld

The O1P/O2P labeling issue is just a little detail I came cross while developing 3DNA. Nevertheless, it serves as an excellent example of the subtleties subtitles that should be taken care of in scientific programming.

Please note that as of 2008, in the remediated PDB/NDB entry adh026, the mislabeled O1P/O2P pair has been correct. More generally, O1P/O2P atoms have now been renamed as OP1/OP2, respectively. 3DNA v2.0 takes care of such naming changes internally; for generated PDB files, however, 3DNA still adopts the conventional O1P/O2P labeling.

Transparency in the peer-review process of scientific papers

In the Nov. 4, 2010 issue of Nature, there is an interesting Comment, titled "Transparency showcases strength of peer review", by Bernd Pulverer, head of scientific publications at the European Molecular Biology Organization and chief editor of The EMBO Journal. In this article, Pulverer "reflects on his experience at The EMBO Journal of publishing referees’ reports, authors’ responses and editors’ comments alongside papers."

The peer-review process of scientific articles has traditionally been a "black box": (anonymous) reviewers' reports, editors' comments, and authors' responses – extremely valuable information in shaping the final form of published papers – are all hidden from public view. In the Internet era, technology (e.g., online space) is no longer an issue. Now The EMBO Journal has led the way, and "the experience has been overwhelmingly positive." Hopefully, other leading journals (e.g., Nature and Science) would follow the example. Afterall, making the peer-review process transparent is an excellent mean to increase the accountability of science and scientific publications.

Overall, this article is well-written, succinct and logical, and it touches an important topic in scientific publication. Over the past few days, I have read several "Review Process Files" accompanying papers I am interested in, e.g., "Recognition of the amber UAG stop codon by release factor RF1", and found them highly revealing.

Publication of scientific programming code

Recently on the Nature website, I read with great interest a news article, titled "Publish your computer code: it is good enough", by Nick Barnes, a professional software engineer:

Freely provided working code — whatever its quality — improves programming and enables others to engage with your research

Clearly the author knows the "trade secret" in scientific programming. He lists several common reasons why scientists are reluctant to share their source code, and then provides his responses:

1. The code is low quality — "software in all trades is written to be good enough for the job intended". All software has bugs. Sharing code would help improve the code itself and advance the research field.
2. Not a common practice — this is going to change or is already changing.
3. Demand for support — "Nobody is entitled to demand technical support for freely provided code."
4. Intellectual property issue — The most value part "lies in your expertise", code not backed by skilled experts is called abandonware. (I cannot agree more with this point.)
5. Polishing code takes time/effort — not need to, just supply, as supplementary materials in a website, the original code used in your publication.

As is evident from the many comments, this assay is well echoed by the community. As an active computational scientist for over a decade, I share mostly the same opinions. Essentially, the transparency of source code is to ensure repeatability of scientific publications. In the field of computational biology (bioinformatics), it is virtually impossible to reproduce exactly a published figure/table without direct access to details, including the source code.