tips for bioinformatics

This was from a talk by Joel Dudley, originally posted by Shirley Wu at http://shirleywho.wordpress.com/2009/02/11/tips-and-tricks-for-software-engineering-in-bioinformatics-talk-by-joel-dudley/.

Quite useful if you want to start programming something...


1. Learn UNIX. It’s quick, it’s powerful, it’s easy to learn. What often takes several lines to code in a scripting language can usually be reduced to a single line on the command line.

2. Be jack of all trades, but master of ONE. That is, be familiar with most programming languages, but be really good at one of them. In the hierarchy of languages, VB and C are more “primitive” while Ruby and Python are most “advanced” - he recommends starting with one of the more advanced languages if you are new to programming. Out of Ruby and Python, Python will probably give you more bang for your buck, due to the smorgasbord of libraries available and broad acceptance (e.g. academic labs, Google). In addition, there are lots of bridges between languages, such as Jython (Java and Python) and JRuby (Java and Ruby) so expert knowledge of one is usually sufficient for you to make a lot of things work practically everywhere.

3. Don’t reinvent the wheel. “Frameworks are your friends.” Take advantage of large existing projects like BioPython/Perl/Ruby/Java, Django, Rails, etc which contain lots of ready to go code for practically everything. Use the internet to find existing code solutions - e.g. Koders is like a Google search for open source code on the web.

4. Learn one text editor really well. Take your pick of Emacs, vi, or a GUI-based editor like TextMate for Macs. The advantage of emacs and vi is that they will be installed on pretty much any system you come across.

5. “Don’t trust yourself”, i.e. use code versioning. Examples are Subversion, CVS, and git. You can even outsource your code hosting with github. Combine this with project management in GForge.

6. Don’t be afraid to use more than 3 letters to define a variable. Having short variable names won’t make the code run faster. It will, however, make the code more difficult for others (and you, 3 months from now) to understand!
Photo by archeon on Flickr

7. Balance architecture and accomplishment. You may be tempted to create something that is complete, elegant, and perfectly structured. This will likely be a waste of time. It’s ok to sacrifice a little bit of structure to get something that actually works.

8. Automate documentation. Documentation is necessary, but it’s a pain to write. So come up with a convention for your headers and make it automatic. Use available tools like Doxygen, JavaDoc, and RDoc, many of which are free.

The above are generic for academic-level software engineering. Some tips that more specifically address high-throughput biomedical computing:

9. Kill the flat file (sort of). This is the most common file format used in bioinformatics, but it hardly lends itself efficient computation. A common task we want to do with the file is read in the data and store it keyed so that we can look up specific pieces of the data later. Hate databases? Cringe at SQL? If you can represent your data as key/value pairs, consider using an embeddable database like the open source BerkeleyDB (now licensed by Oracle), which require no administration. If you don’t mind SQL, but hate the administration, SQLite allows you to create embedded, serverless databases. Other options that go beyond the relational database concept are CouchDB (”a distributed, fault-tolerant and schema-free document-oriented database accessible via a RESTful HTTP/JSON API”) and Hypertable (”a high performance distributed data storage system”).

10. New ways to do parallel computing. Determine whether your tasks are loosely coupled (independent) or tightly coupled. Although personal computers and laptops are coming out with more cores, most programs only use one at a time. Find ways to utilize idle cores - e.g. there is a way to do this in R. Think in terms of MapReduce. Take advantage of cloud computing, like Amazon’s EC2. Use platforms like Hadoop and Disco to make parallel computing applications. A cool example of this is Cloudburst-Bio, a massively parallel project for genome assembly from next-generation sequencing that uses MapReduce.

11. Embrace hardware. New (and old) hardware is available that can give you significant speedups in biomedical computation, notably graphical processing units (GPUs) which have been used to accelerate molecular dynamics. Hardware vendors like Nvidia are starting to respond; you can now get GPU workstations like NVidia’s Tesla personal supercomputer offering many 100sX speedup over traditional workstations. So if you don’t want to utilize the cloud, you can get an affordable and powerful cluster that fits on top of your desk. Aside from GPUs, there are field programmable gate arrays - chips you can program after manufacturing.

12. Playing nice with others. Think a bit about data exchange formats - but definitely use them! Suggestions are JSON, YAML, and, of course, XML. When working in teams, use an “agile software development” strategy - mainly many fast iterations of the specification-development-feedback cycle. Use tools to automate the development process, such as unit testing and the granddaddy, “make“. Tools like BaseCamp (and perhaps Science 2.0 versions like Laboratree) can help with the more general project management aspects.

————————————————-

In summary:

Focus on the goal (biology or medicine).
Don’t be clever (you’ll trick yourself).
Value your time.
Outsource everything but genius.
Use tools available to you.
And have fun. ;)


Slides for Joel’s presentation are up on Slideshare http://www.slideshare.net/jtdudley/tips-and-tricks-for-bioinformatics-software-engineering.

by Beyond Lab

tough decision - how to focus

Like any graduate students doing research, there are some tough times. This is what I am going through recently. --The balance between research and family; the requirements of department to meet; the struggling to focus on only one project.

Looking back, I have to admit that I have not been very focused on my research. As a result, I have worked on 4 or 5 different projects. They are all excited projects. And I have made reasonable progress in most of them. But now I realized that to graduate quickly, I have to focus on one thing and do something deep enough. So, which project to drop?? I am struggling between two projects. The one I have made most progress and have produced quite a publication is really risky to follow up and should definitely have big impact (this is like marketing). The other one is relatively straightforward (I have to say relative) and will very likely generate some small paper(s).

Plus, the department required me to teach for two semesters --one of them has to be some kind of lecturing (like lab courses). This will definitely eat out a lot of my time in research.

I wish I had 48hours a day to work!!!

I think I probably will go with the relatively easier one so that I can graduate by the end of next year. After graduation, if the risky one has not been published by other researchers, I could continue it. (Again, this is marketing!!!)

Wish me luck!

by Beyond Lab

lab design

For most biology research (especially molecular biology), lab design is an art. Poorly designed labs will "effectively" limit your productivity, including moving around, organizing equipment, communication, storage, wasting space, etc. All these things must be considered. In order to do that, the actual researchers have to be actively involved.

Our lab has moved a few times in the last two years, either moving across states, or from one building to another building. The building I am currently in is brand new. But we've already seen a lot of design problems.

To name a few:
1. No storage space. Biology research utilizes a lot of tubes, dishes, and so on. It is impossible to buy new one every day or every week. So, you always buy in boxes, even in 10-20 boxes each time. Therefore you have to have space to store them. However there is absolutely no space designed for this purpose. As a result, our lab manager had to personally buy shelf material from Home Depot and ask carpenter to put shelves on the walls, which are not as stable of course, but is much better. Now, everytime our big boxes come, we have to unpack them and put the contents onto the shelves (obviously the boxes are too big for regular shelves).

2. curtain and emergency light for microscopy room. Modern microscopy mainly refers to fluorescent microscopy. This requires dim or no light while working --means dark room. This was designed badly with an emergency light right above the microscope. It is emergency light, you have to leave it on all the time -- how do you use the microscope then since darkness is needed? Also microscopy rooms usually have curtains to block lights out. Ironically they designed white curtain for dark room!

3. Conference room. You have to present your powerpoint slides - always with images - so you want the lights in the conference room adjustable. This was designed. However, the rooms have two big windows facing south. The regular blinds let lights in easily. Bad hah. This is worse -- the room is about 2 meters wide and 5 meters long with the screen installed at the long side. You know what I mean, when you want to see the presentation, you have to bend your whole body back. No one's neck likes that. If there are more than 5 people, you'll have to watch the presentation half meter in front of the screen. Like it?

There are more...

Who the hell designed the building???





by Beyond Lab

another stupid microsoft thing

Have you ever tried to set up two internet connections for your labtop? --Are you tired of changing between static IP address and DHCP?

Will, microsoft actually has this function. How to use it? -- This is the help page.
http://support.microsoft.com/kb/283676

Follow this, can you find the "alternative configuration" tab??

If you are lucky, you will see it. But very likely you don't see it. --Why? Simple! It only shows up if you select DHCP (automatical). If you set a static IP etc., there is no alternative configuration tab.

Why? Ask Bill Gates. (Oh, I guess he's off the hook already. But sorry, we have to blame him.)


by Beyond Lab

better than others?

Something I am doing right now requires me to demonstrate that I am better than others with the ame levels of education. What thing I can do but others cannot?

While thinking about this question, I remember something like "if you cannot describe what you are doing in one sentense, stop doing it. you are wasting your time."

Sure I can do that. But my training has been a bit diverse, although always in life science -- from medical school gradually shifted toward basic pathology research to current biological research. I'll have to explain some basics before people really gets what I am doing. On the other hand, this really gives me something special than others. I will have to take advantage of my training background.

However, I understand that to succeed, it is necessary to be able to clearly explain to lay people my research in PLAIN language. So that people understand the importance of my research and therefore provide support. This is not just grant writing, which is for experts to review. This is for everyone else. I will post it here once I am done.


by Beyond Lab

DNA for dating??

by Beyond Lab

It has always been said that it is chemistry brings two people together. Probably it is right (lol) - check out this site: http://www.genepartner.com/ .

When doing transplant, you always need to match certain genes for example MHC, but in the future, before date someone, test his/her DNA first. --Or try to steal some of stuff he used on your first date to get the DNA tested.

This is a joke. --That's all I can say.

But will the company profit? probably. There are enough idiots in this world. Only marketing matters in business.

where is your saliva samples being analyzed?

by Beyond Lab

it is clear that 23andme uses Laboratory Corporation of America (LabCorp) as its genotyping service lab with Illumina chips (arrays). --Beyond lab is wondering how much 23andme will pay LabCorp for each sample, how much is the chip and how much can they get from what customres pay. --This market is huge but is absolutely quantity-dependent. The more customers, the more profit. What will the customres get and how will the information help the customres? --that's something else.

money, money

by Beyond Lab

Research is extremely expensive -- even more than drug development. NIH is throwing $8 million to epigenome and human disease studies, starting next year. Is this a big amount? No. absolutely not. it is just a few R01 grants. Epigenetic studies require a lot of new/expensive equipment and techniques, such as microarray, sequencing. in many cases, new methodologies have to be developed. Also, when focusing on human diseases, it needs more resource input.

More importantly, epigenetics is an expanding area with new markers appearing one by one. Which one of the epigenetic markers is more important? How could $8 million be balanced properly to all these markers?? WE NEED MORE!!!

Hopefully this is just the beginning.

useful links

by Beyond Lab

http://sciencecareers.sciencemag.org/career_development/previous_issues/articles/2006_10_20/mastering_your_ph_d_giving_a_great_presentation/

http://sciencecareers.sciencemag.org/career_development/previous_issues/articles/2008_03_28/caredit_a0800045

summer vacation and protection

by Beyond Lab

There are a lot of reasons to avoid exposure to strong sunshine. This should be especially noticed during this summer travel time. -- Being tan might make you look good and feel good. But does your body feel good as well? -Most likely not.

There is clear scientific connection between heavy sunburn and melanoma (a kind of skin cancer) occurrence. People received multiple severe sunburns are at higher risk of developing melanoma. Children are at even higher risk.

Protect yourself and your family by doing necessary things, high SPF sunscreen (and reapply every 2 hours if in heavy sunshine), protective clothing and hats, and so on. What's the best solution? -- avoid the sun during peak hours -10am to 2pm.

Just my 2 cents.

A graduate student oath -- will it help?

by Beyond Lab

University of Toronto created a graduate student oath to let the students remember their social and moral responsibilities, in other words, to conduct research ethically. I think one of the reasons is to try to avoid so many scientific misconduct in the scientific research area. To name a few, the Korean tem cell scandal, the recent retract of an important paper by Linda Buck, a Nobel prize laureate. There are not only irreproducibility of their data, but also the way they put all responsibility to one of the co-first authors. All these are absolutely not normal and should not happen in the pursuit of science.

Will this oath help? I completely doubt it. -- The overall scientific environment is so competitive, mainly financially, that researchers have to publish before their competitors and have to publish in good journals to secure enough support for their continuing research, and their personal salary in many cases.

Is there any way out? Things have to be changed gradually. Higher NIH budget (in US) is definitely one of the first things to do.

what's wrong with those consumer genomics companies?

by Beyond Lab

After the action of New York state about 2 months ago, California is taking a similar approach to try to regulate consumer genomics (personal genomics) companies from offering genome services without prescription from doctors. With many posts in my blog talking about the current situation of personal genomics, you might understand that one of the basic reasons is that it is not ready yet. (Most) Consumers feel what they got from the services didn't worth the money. As many experts suggested, the current consumer genomics services should be considered as "recreational genomics" -- therefore whichever company marketing these services should not relate them to health or medical implications. Otherwise, you have to get physician's prescription. So, at this point, it is reasonable for New York and California two states to initiate some regulations.

This is a good thing!

to make use of genome

by Beyond Lab

Human genome is huge. Individual variations are also extremely common. Most of these variations don't have any effect on any function. But some, either by itself or in combination with others, do. What, how, when, and where these variations matter is something we have to know before personal genomics really mean anything.

As one of my earlier posts indicated, some companies, in collaboration with research institutes, have projects on their target diseases or conditions. But that's obviously not enough. We have to know everything - eventually.

So, there is a "genome-wide association studies" from NIH which involves "rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease". Many diseases are under study now. This sort of "national" or global initiative, like the previous human genome project, is really the drive to our understanding of our genome and therefore could make use of genome information.
More detail information could be found here: http://www.fnih.org/GAIN2/home_new.shtml

One gene, one disease??

by Beyond Lab

Obviously not. Life is so complicated that it is impossible for one gene to be solely responsible for one function and therefore one disease. Almost all genes identified have multiple domains (function units) with different "potential" function. So, mess up one gene would certainly have more than one consequences. This has been confirmed in many species, from bakers yeast to human.

So, it is almost impossible to predict the occurrence of one disease just by analyzing the function/structure of one gene or its product. It has to be a combination of various information. With that being said, is it helpful to analyze one gene if it is know that this particular gene (or its mutant formats) always associates with certain disease. Absolutely!. But how accurate is it? No one knows when it comes to one individual -- yes or no. Probability means nothing for one individual.

Why am I saying this? Because one company Orion Genomics just licensed JHU technology to analyze IGF2 gene (insulin-like growth factor 2) with the hope to be able to predict the outcome (progression) of colorectal cancer. -- Beyond Lab personally thinks this is not very wise. I don't know how they will promote their future product to analyze one single gene. --Most current genetic or genomic detection products for breast cancer all involve many genes. One gene? Unlikely mean anything.

More on presentation

by Beyond Lab

Last month's Nature Methods had an editorial named "talking points".

The short list of advice is:
1. Plan for the allotted time.
2. Know your audience.
3. Define your goals.
4. Structure your talk.
5. Keep your slides simple (content).
6. Keep your slides simple (design).
7. Beware of animations and multimedia.
8. Watch your delivery.
9. Choose your words.
10. Rehearse!

One thing Beyond Lab wants to point out here is that it once again recommends serif font just as Tomjoe's comment to one of my earlier posts.

So, use it!!!

Big money on personalized medicine

by Beyond Lab

Luxembourg government decided to take the challenge to push personalized medicine researches with big money. In collaboration with three U.S. institutes, U. of Luxembourg will establish several research centers to build a BIOBANK which collects huge amounts of disease samples and genetic information. This proposed system will be used to promote translational research and systems biology and in the long run will build the basics for personalized medicine. Of course, this has to be helped with modern personal genomics studies.

To Beyond Lab, this initiative is an important step toward personalized medicine. With U.S. economy going slow and U.S.federal funding being flat, other countries like Luxembourg, Japan, Singapore, and even South Korea are putting big amount of money in life science. At this point, the whole thing is still at data/information collection stage. But very soon, really useful knowledge/technology will come out and some of them will bring money back to those countries who invested in the research. Although it is difficult to predict exactly a time frame, the fast growing technologies will sure prove this is the case.

Personal genomics -- not only cancers

by Beyond Lab

A significant part of personal genomics studies have been focusing on the relationship to cancers. But that's definitely not the whole case. Recent gene analysis showed the potential use of personal genomics in other diseases related to our everyday life such as metabolic disorders -- folate (a kind of vitamin) metabolism.

Sequencing of a vitamin-dependent enzyme (critical proteins which carry out most of the molecular reactions in our body) methylenetetrahydrofolate reductase (MTHFR) from about 600 persons' genomes found that there are some variations in the populations. Some of the variations actually affected the enzyme function. More importantly, increasing folate level could rescue its function to normal level. --This is really direct evidence that simply changing what we eat everyday could interact with personal genomes and therefore have obvious benefit.

How useful is your personal genomes? Studies like this will gradually prove it. - Some time in the future, sequencing your genome will be like buying a car. Of course, by then genomics counselors will be a good job :)

colorectal cancer and patient personal genomics

by Beyond Lab

Here, another example showed that colorectal cancer patients with normal K-RAS gene have better response to a FDA approved drug (an EGFR antibody if you are interested).

The study was a multi-center multinational prospective clinical trial (Phase II) of Cetuximab where about 600 colorectal cancer patients were examined for K-RAS gene mutations and related to response to drug treatment (in combination with standard chemotherapy). --More wild-type K-RAS carriers showed reduced cancer and decreased risk of cancer progression. The numbers are not dramatic, but are significant considering the number of patients studied.

This kind of study will gradually build the foundations of personalized medicine and the eventual application of personal genomes (genomics). As mentioned in one of my previous posts, those personal genomics companies should collaborate with researchers to expand this kind of correlation studies (especially with NIH funding is limited).

new marketing strategy: RESEARCH

by Beyond Lab

You have probably already heard that 23andme established a collaboration with Parkinson's Institute to work on a system to use computer and internet to assess the relationship between patients' medical information, genes and Parkinson's Disease. This is not only a completely new thing to everyone, but also a very clever way to promote the companies' personal genomics services. Research to promote business -- Hasn't this been going on for a long time except no involvement of computers and internet.

Because it is so new, a lot of ideas need to be developed by the collaborators. They need to prove the principle actually works. Just to name a few challenges: an internet based information collection, analysis and distribution system (which is far mor complicated than a conventional database); a way to use this information and personal genomes securely; how to expand to other disease models for example diabetes ...

Although Beyond Lab has no doubt of the potential success, it takes time to let both the academics and general community accept the concepts. Let's keep an eye on it.

personal genome service in China

by Beyond Lab

Last year my brother had chances to interact with several personal genomics companies in China. From his first hand experience, I briefly describe the situation of industrialization of personal genomics services in China. There seem to be some success in terms of marketing in this premature market.

There are about 4~5 private companies promoting sequencing genome for individuals. The most success one was established by several marketing experts. Among those are an editor China Daily news paper press, a marketing specialist (who is the president), a graduate student of Peking University (this is the only “scientist”), a novel writer, a lawyer. What's obvious from this combination is that they are good at marketing. In fact, according to them, they've sell up to 300 million Chinese Yuan of personal microarray genomic services in about one year last year. Their "success" also relies on another factor -- China has 1.4 billion people and the rich have too money to consume. Those rich people are keen to try new technology even if they don't understand it at all. This is called "fashion".

Their marketing strategy is massive media broadcasting and training workshops. They take advantage of the fact that so many people are looking for chances to make money and so many people can be easily talked into new things. So, they recruit a lot of distributors, who have to pay them a certain amount of money to join，to do the actual person-to-person marketing in hospitals and health related business areas. They are quite successful so far.

Another company takes a different approach. They collaborate with one academic organization to promote personal genomic services to children. Since children are parents' future and main focus, people are willing to pay for this kind of new things such as a microarray analysis if breast cancer related genes etc.

Still one more company is trying a governmental approach. The company director established some relationship with Department of Health of central government and persuaded the Department to develop a suggestive medical protocol for genetic testing in favor of this companies' product (one of which is similar to above breast cancer microarray). Once this protocol is distributed to hospitals, there will be doctors prescribe these related tests. How good is this approach? There is not enough data yet. But it is certainly interesting to follow up.

I don't know any company is providing SNP personal service in China as of now.

You may find some of these are special to China. But this is still the beginning of the field. Marketing of personal genome service is a challenge around the world.