Kuo-Chen Chou talks with
ScienceWatch.com and answers a few questions about
this month's New Hot Paper in the field of Biology &
Biochemistry. The author has also sent along images of
Article Title: Recent progress in protein
subcellular location prediction
Journal: ANAL BIOCHEM
Year: NOV 1 2007
* Gordon Life Sci Inst, San Diego, CA 92130 USA.
* Gordon Life Sci Inst, San Diego, CA 92130 USA.
(addresses have been truncated)
Why do you think your paper is highly
Information on the subcellular locations of proteins is important because
it can provide useful insights about their functions, as well as how and in
what kind of cellular environments they interact with each other and with
other molecules. It is also fundamental and indispensable to systems
biology because knowledge of the localization of proteins within cellular
compartments can help us to understand the intricate pathways that regulate
biological processes at the cellular level.
Although the subcellular locations of proteins can be determined by
conducting various biochemical experiments, the approach by purely doing
experiments is both time-consuming and costly. In particular, the number of
newly-found protein sequences has been explosively increased. For instance,
in 1986, the Swiss-Prot databank contained merely 3,939 protein
sequence entries, but the number has since jumped to 408,099, according
to version 56.7 of January 20, 2009, meaning that the number of protein
sequence entries now is more than 103 times the number from about 23
22 different components or organelles in a
View/download two accompanying
With the avalanche of gene products generated in the postgenomic age, the
gap between newly-found protein sequences and the knowledge of their
subcellular localization is becoming increasingly wide. Therefore, it has
been highly desirable to develop computational methods by which one can
quickly predict the subcellular locations of proteins, based on their
sequence information alone.
During the past 15 years or so, many predictors have been developed in this
regard. Our paper was focused on recent advancements, particularly on those
predictors that distinguish themselves by having some remarkable features,
such as the ability to be able to deal with proteins having multiple
subcellular locations, the state-of-the-art prediction engines, the
rigorous procedures for constructing high-quality organism-specific
benchmark datasets, and the user-friendly web-servers accessible to the
public. These features might be the reason for the paper being highly
Does it describe a new discovery, methodology, or
synthesis of knowledge?
The paper did describe several new concepts and methodologies, such as
pseudo amino acid composition, or PseAA composition, hybridization of the
"higher level" approach with the ab initio approach, ensemble
classifier, and how to deal with multiplex proteins which may
simultaneously exist at, or move between, two or more different subcellular
locations. Proteins with multiple locations or dynamic features of this
kind are particularly interesting because they may have some special
biological functions intriguing to investigators in both basic research and
areas of drug discovery.
Would you summarize the significance of your paper
in layman's terms?
A cell is the most elementary unit of life. Its survival and replication
will depend on the proper functions of many proteins therein; while the
latter will depend on whether they are correctly located in their
compartments or organelles (see Fig.1
[.PDF file]), called subcellular locations. It may
cause various strange diseases should they occur at the wrong location
sites. Therefore, one of the fundamental problems in cell biology and
proteomics is to identify the subcellular locations and functions of
these proteins, the cell's primary machinery.
To address this problem, a user-very-friendly web-server package called
Cell-PLoc is described. It is freely accessible to
the public via the web site. Cell-PLoc contains six predictors:
Euk-mPLoc, Hum-mPLoc, Plant-PLoc, Gpos-PLoc, Gneg-PLoc, and Virus-PLoc,
specialized for eukaryotic, human, plant, Gram-positive bacterial,
Gram-negative bacterial, and virus proteins, respectively (see Fig.2
For example, by using Euk-mPLoc, one can easily predict the subcellular
location site(s) of a specific eukaryotic protein among the 22 possible
location cites, as illustrated in Fig.1, with a high expected accuracy, in
only about five seconds. Readers can also find a step-to-step guide for how
to use the Cell-PLoc package in a recent protocol article (Chou KC, et
al., "Cell-PLoc: a package of Web servers for predicting subcellular
localization of proteins in various organisms," Nature Protocols:
3: 153-62, 2008).
How did you become involved in this research, and
were there any problems along the way?
I was engaged with this research when I worked with the Pharmacia &
Upjohn Pharmaceutical Company, because it could provide very useful
information for drug discovery, and many project teams often came to my
office asking about essentially the same question. This led me to design a
web-server for predicting protein subcellular localization. Of course, it
was available only within the company and its power was quite limited.
After Pharmacia was merged with Pfizer in 2003 and I left the company, in
collaboration with Dr. Hong-Bin Shen, my postdoc from Shanghai Jiaotong
University, we eventually established the current Cell-PLoc which is much
more powerful and freely accessible to the public.
Where do you see your research leading in the
We are prepared to establish a much more complete web-server package which
can more efficiently predict protein subcellular localizations by covering
a wider scope and increasing the accuracy expectancy, while also predicting
all the other protein attributes.
Do you foresee any social or political implications
for your research?
The social implications I have foreseen is that publicly accessible
web-servers will become more and more popular and these will have important
impacts not only on science but also on the economy and other aspects of
Kuo-Chen Chou, Ph.D.D.Sc.
Gordon Life Science Institute
San Diego, CA, USA
Shanghai Jiaotong University
Shanghai, P. R. China Web