Using bioinformatics to identify novel caspase substrates
Caspases are a family of cysteine proteases, which cleave proteins next to an aspartate residue. The members of this family play essential roles in regulating programmed cell death (apoptosis) (Pop C. & Salvesen GS. 2009).
In addition to their established function in cell death, a variety of recent publications have provided increasing evidence that apoptotic caspases also participate in several non-apoptotic cellular processes. Activated caspases exhibit functions during T-cell proliferation, cell cycle regulation, and the differentiation of a diverse array of cell types.
Recently our lab has developed new software that we call Caspase-3 Tool (CAT3). CAT3 is a powerful bioinformatic tool that can predict the cleavage site of caspase-3 substrates with accuracy higher than any other similar software. CAT3 successfully predicts 90.8% of randomly chosen substrates that their cleavage sites are experimentally determined.
CAT3 will be used to carry out high throughput analysis for protein sequences of various pathogenic species. The focus will be on the infectious microbes that propagate inside the cells of immune system.
The results of this project are expected to reveal novel capase-3 substrates and/or natural inhibitor that exists in these microorganisms.
Researchers: Yaqoub Ashhab, Muneef Ayash, Hashem Tamimi
Developing a Powerful In Silico Tool for the Discovery of Novel Caspase-3 Substrates: A Preliminary Screening of the Human Proteome. Ayyash M, Tamimi H, Ashhab Y. BMC Bioinformatics. 2012 Jan 23;13(1):14.
The idea of the project is to develop a user friendly knowledgebase that contains all proteins that are cleaved by caspase enzymes.
The proteins are graphically represented to facilitate the analysis and studying of caspases substrates. Each protein file contains rich information such as the cleaving caspase(s), the exact cleavage position, functional domains, biological implications of the cleavage process, and links for the pathway and interaction for each protein.
The database offers easy to use searching tools that allow simple as well as advanced search. The database will be freely available via a web site through Palestine Polytechnic University’s server.
The unique feature of this database is its ability to evolve through the contribution of browsers (biologists) from all around the world. The browsers can contribute to grow the database through adding more caspase substrates or editing already available data. The contributions of browsers were designed in a way to ensure high security data entry as well as to minimize effort needed by the administrators to follow-up and validate the contributions.
In addition, our database is capable to automatically and regularly update all its content based on recent data that is available through various central databases such as Uniprot and PubMed.
Researchers: Yaqoub Ashhab, Mahmoud Al-Saheb, Hani Qudsi, Abed Al-Rahman Haddad, Islam Itkaidek, Hashem Tamimi, Hasan Al-Taradeh
Developing a new bioinformatic tool to perform high-throughput analysis and comparison of bacterial proteoms
The availability of enormous amount of genomic data generated from various sequencing projects provides a great opportunity for researchers to study and infer the desired functional information. Bioinformatics-based approaches have proven powerful and cost-effective means to study and represent huge genomic and proteomic data from bacterial genomic projects.
Most system biology-based computational tools that aim at exploring and comparing biological sequences of prokaryotes focus on genomic data. Such tools usually perform similarity comparison that doest not take into account the differences between genomes. There is an increasing need to develop genomic and proteomic tools that shed light on the similarities and differences alike. Such methods would allow more accurate classification of bacteria that are based on whole proteome or genome instead of a single gene such as 16SrRNA.
In addition, a comprehensive analysis and comparison of various bacterial proteomes can help in assigning functions for many hypothetical proteins that are still annotated as proteins with unknown functions in the biological databases.
This project presents a novel approach for developing an intelligent tool that can perform a high-throughput comparison and mapping to reveal similarities and differences among bacterial proteomes. The developed software is capable to visualizing the relationship between different types of bacteria based on Self Organizing Map method. The idea is to compare any given bacterial proteome with a set of essential proteins known here as a core proteome. The core proteome can be defined as the minimum set of proteins that are hypothetically essential to form a fully functional bacterium
Researchers: Yaqoub Ashhab, Hashem Tamimi, Bilal Tamimi
BACTOSOM-Viewer: a High-Throughput Bacterial Mapping Tool Based on Landmark Proteins. Bilal Tamimi1, Sami Salamin, Hashem Tamimi, Yaqoub Ashhab. 2nd Conference on Biotechnology Research and Applications in Palestine, 26-27th September, 2010.