As the database size and the genomic proportion continue to grow, it is more likely that a misconfigured search would encounter CPU and HSP related errors. Here are some general suggestions in coping with such type of errors:
a. Reduce the size of the query by breaking a large query into smaller chunks and search with each smaller chunk indivivually.
b. Search a smaller and well curated database or a more relevant subset of the original database using ENTREZ_QEURY parameter.
c. Increase the search stringency by using smaller EXPECT, larger WORD_SIZE, and more appropriate FILTER settings.
d. Use a more stringent algorithm if applicable.
For identification of candidate genes contained within a nucleotide query sequence, a recommended way to search is to gradually escalate the search intensity. Use megablast first, followed by discontiguous megablast, blastn, and blastx. Proceed to next algorithm if the result from a strigent algorithm is not informative. The tblastx search should be reserved as the last resort and it should always be combined with ENTREZ_QUERY to focus the search to a more relevant subset of the target database.