6533b863fe1ef96bd12c794a

RESEARCH PRODUCT

In silico strategy for detection of target candidates for antibody therapy of solid tumors

Gerd HelftenbeinGerhard SeitzMichael KoslowskiUgur SahinKarl DhaeneÖZlem Türeci

subject

RNA Messenger/geneticsDatabases Factualmedicine.drug_classIn silicoAntineoplastic AgentsBiologyMonoclonal antibodyComputational biologyNeoplasmsNeoplasms/immunologyGeneticsRefSeqmedicineHumansRNA MessengerGeneAntibodies Monoclonal/immunologyGeneticsExpressed Sequence TagsExpressed sequence tagReverse Transcriptase Polymerase Chain ReactionAntineoplastic Agents/therapeutic useAntibodies MonoclonalGeneral MedicineTumor antigenGenes/physiologyGene expression profilingTransmembrane domainGenes

description

In contrast to earlier attempts for the identification of target candidates suitable for monoclonal antibody (mAb) based cancer therapies we concentrated on highly selective lineage-specific genes additionally preserved or even overexpressed in orthotopic cancers. In a script aided workflow we reduced all human entries of the RefSeq mRNA database to those encoding transmembrane domain bearing gene products and subjected them to BLAST analysis against the human EST database. All BLAST results were validated in a gene centric way allowing two types of data curation prior to expression profiling of matching ESTs in selected healthy tissues: (i) exclusion of questionable ESTs arising e.g. from genomic contamination and (ii) elimination of erroneously predicted mRNAs as well as transcripts with only weak EST coverage. The impact of such stringent input control on accuracy of prediction is underlined by RT-PCR confirmation of predicted tissue distribution patterns for a number of selected candidates.

10.1016/j.gene.2008.02.009https://doi.org/10.1016/j.gene.2008.02.009