Navigation Links
Faster, more accurate, more sensitive
Date:12/25/2011

Lightning fast and yet highly sensitive: HHblits is a new software tool for protein research which promises to significantly improve the functional analysis of proteins. A team of computational biologists led by Dr. Johannes Sding of LMU's Genzentrum has developed a new sequence search method to identify proteins with similar sequences in databases that is faster and can discover twice as many evolutionarily related proteins as previous methods. From the functional and structural properties of the identified proteins conclusions can then be drawn on the properties of the protein to be analysed. "Our method will expand the scope and power of sequence analysis, which will in turn facilitate the experimental elucidation of the structure and function of many proteins", says Sding, who is also a member of the Center for Integrated Protein Science Munich (CiPSM). (Nature Methods, 25.12.2011)

Proteins are involved in nearly all biochemical processes of life. The functions that a protein performs largely depend on the sequence of the 20 amino acid building blocks and on the three-dimensional spatial structure into which this sequence of amino acids folds. From the similarity of protein sequences, bioinformatic methods can predict their evolutionary relatedness, which in turn implies similar structure and functions. Therefore, proteins to be studied are standardly subjected to a sequence search, in which their sequence is compared with millions of sequences in public databases with annotated structures and functions. The properties of the protein of interest can then be inferred from the properties of the proteins with similar sequences, including its structure and functions. The general relationship between sequence and function makes it possible to predict the structure and function of a given protein by comparing its sequence with those of proteins of known structure/function. Publicly accessible databases exist in which the sequences of known proteins are stored, together with information on their biological functions, which facilitates such comparisons. "This kind of sequence analysis is a fundamental tool in the field of bioinformatics," explains Sding.

The sequence search programs assess sequence similarity by computing pairwise alignments: the two sequences of amino acids are arranged one above the other in such a way that mostly identical or similar amino acids are paired up in the same columns. "Perhaps even more important than the search for pairwise sequence similarities is the assembly of so-called multiple sequence alignments; in this case one searches for similar sequences in many related proteins and arranges them into a matrix, in which each sequence fills a row and similar amino acids end up in the same columns" says Sding. Because the functions and structure of evolutionarily related proteins are generally conserved - i.e. preserved even when the sequence is altered by mutations during the course of evolution - multiple sequence alignments form the basis for the prediction of the structure and molecular functions of uncharacterized proteins.

For the past 15 years, the program PSI-BLAST has been the most popular tool for the comparison of protein sequences, as it combines speed with high sensitivity and precision. Now Sding's team has designed a method, called HHblits, which clearly surpasses PSI-BLAST in all aspects of performance. This improvement is largely due to two factors. First the researchers convert both the sequence of interest and the sequences in the database to be searched into so-called Hidden Markov Models (HMMs). HMMs are statistical models that incorporate the mutation probabilities determined from sequence alignments so this step increases the sensitivity and precision of the subsequent similarity search. In addition, the team has developed a filtering procedure that allows them to reduce the amount of data that needs to be searched without appreciable loss of sensitivity. The trick is first to assemble similar sequences from the database into multiple sequence alignments. Each alignment column is then labeled with one of 219 "letters", such that columns with similar amino acid composition are represented by the same letter. "By translating the multiple sequence alignments into sequences composed of these 219 letters, we can replace the time-consuming pairwise comparison of HMMs by the comparison of simple sequences", says Sding. This reduces the search time 2500-fold. Sding emphasizes that "HHblits allows to predict the function and structure of proteins more often and more accurately than was previously possible." His group is already working on further improvements to the method, for example by incorporating information on the three-dimensional structures of proteins. (gd)


'/>"/>
Contact: Simon Kirner
simon.kirner@lmu.de
49-892-180-3174
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

Related biology news :

1. UBC megapixel DNA replication technology promises faster, more precise diagnostics
2. ASU scientists develop universal DNA reader to advance faster, cheaper sequencing efforts
3. Boston University reseachers develop faster, cheaper DNA sequencing method
4. Faster, cheaper way to find disease genes in human genome passes initial test
5. Faster, more cost-effective DNA test for crime scenes, disease diagnosis
6. Forsyth scientist receives major grant to support rapid, accurate, affordable test for tuberculosis
7. Orca ears inspire Stanford researchers to develop ultrasensitive undersea microphone
8. Oceans harmful low-oxygen zones growing, are sensitive to small changes in climate
9. LSUHSC study IDs proteins regulating water retention in salt-sensitive hypertension
10. Globalized economy more sensitive to recessions
11. New artificial skin could make prosthetic limbs and robots more sensitive
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/22/2016)... June 22, 2016   Acuant , ... verification solutions, has partnered with RightCrowd ® ... for Visitor Management, Self-Service Kiosks and Continuous ... that add functional enhancements to existing physical ... and venues with an automated ID verification ...
(Date:6/21/2016)... British Columbia , June 21, 2016 /PRNewswire/ ... appointed to the new role of principal product ... been named the director of customer development. Both ... NuData,s chief technical officer. The moves reflect NuData,s ... teams in response to high customer demand and ...
(Date:6/16/2016)... The global Biometric ... USD 1.83 billion by 2024, according to a ... proliferation and increasing demand in commercial buildings, consumer ... the market growth.      (Logo: ... of advanced multimodal techniques for biometric authentication and ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... --  Ginkgo Bioworks , a leading organism design ... awarded as one of the World Economic Forum,s ... innovative companies. Ginkgo Bioworks is engineering biology to ... in the nutrition, health and consumer goods sectors. ... including Fortune 500 companies to design microbes for ...
(Date:6/24/2016)... DIEGO , June 24, 2016 ... more sensitively detects cancers susceptible to PARP inhibitors ... circulating tumor cells (CTCs). The new test has ... HRD-targeted therapeutics in multiple cancer types. ... targeting DNA damage response pathways, including PARP, ATM, ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Researchers at the ... commonly-identified miRNAs in people with peritoneal or pleural mesothelioma. Their findings are the subject ... it now. , Diagnostic biomarkers are signposts in the blood, lung fluid or ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... to announce the launch of their brand, UP4™ Probiotics, into Target stores nationwide. ... years, is proud to add Target to its list of well-respected retailers. This ...
Breaking Biology Technology: