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+# ===========================================================================
+#
+#                            PUBLIC DOMAIN NOTICE
+#               National Center for Biotechnology Information
+#
+#  This software/database is a "United States Government Work" under the
+#  terms of the United States Copyright Act.  It was written as part of
+#  the author's official duties as a United States Government employee and
+#  thus cannot be copyrighted.  This software/database is freely available
+#  to the public for use. The National Library of Medicine and the U.S.
+#  Government have not placed any restriction on its use or reproduction.
+#
+#  Although all reasonable efforts have been taken to ensure the accuracy
+#  and reliability of the software and data, the NLM and the U.S.
+#  Government do not and cannot warrant the performance or results that
+#  may be obtained by using this software or data. The NLM and the U.S.
+#  Government disclaim all warranties, express or implied, including
+#  warranties of performance, merchantability or fitness for any particular
+#  purpose.
+#
+#  Please cite the author in any work or product based on this material.
+#
+# ===========================================================================
+
+
+The NCBI SRA ( Sequence Read Archive )
+
+
+Contact: [e-mail]
+http://trace.ncbi.nlm.nih.gov/Traces/sra/std
+
+
+Stand-alone BLAST searches against SRA runs in their native format.
+-------------------------------------------------------------------
+
+A stand-alone blastn application to perform BLAST searches directly against 
+native SRA files is included in this distribution. This application has been
+tested in-house at the NCBI, but has not been heavily used, so this should be
+considered a preliminary (alpha) release to a few experienced users. A 64-bit
+LINUX application has been built for this testing. 
+
+The application is called "blastn_vdb".
+
+The application can be invoked in much the same manner as the standard 
+blastn application:
+
+1) blastn_vdb -help or blastn_vdb -h will produce usage messages.
+
+2) The BLAST+ command-line manual at http://www.ncbi.nlm.nih.gov/books/NBK1763/ 
+provides more details on the options, though not all blastn options are
+available with blastn_vdb. Some options simply do not apply to sequences in SRA
+(e.g., -gilist is missing as these sequences have not been assigned GI's). Some
+options have not yet been implemented (e.g., -num_threads is currently disabled).
+
+
+To search cached or on-demand SRA objects.
+------------------------------------------
+An example blastn_vdb command-line would be:
+
+./blastn_vdb -db "ERR039542 ERR047215 ERR039539 ERR039540" -query nt.test -out test.out
+
+The file nt.test contains the query in FASTA format, and it will be searched against 
+the reads in runs with accessions ERR039542 ERR047215 ERR039539 ERR039540.
+
+If you have not already downloaded these objects using the vdb "prefetch" tool,
+they will be retrieved on-demand from NCBI under standard configuration. For
+alternative configuration information, please see the "README-vdb-config" file
+in this distribution.
+
+Searching with manually downloaded files.
+-----------------------------------------
+If you have manually downloaded files, e.g. via aspera or wget, etc., they may
+be referred to as "local" files. You can pass one or more file paths to be used
+collectively as the database. In this case the blastn_vdb command-line would be:
+
+./blastn_vdb -db <SRR_file> -query <input_file> -out <output_file>
+	
+Where
+<SRR_file> is the path (relative or absolute) and name of the SRRxxxxx file
+<input_file> is a fasta file containing the sequence(s) to be BLASTed
+<output_file> is the name specified for the output report of the blast search.
+
+Example:
+
+./blastn_vdb -db ./subdir/ERR039542.sra -query nt.test -out test.out
+
+Querying multiple SRR files simultaneously:
+
+./blastn_vdb -db "<SRR_file1> <SRR_file2> <SRR_file3>" -query <input.fa> -out <output_file>
+
+Enclose the group of files to be included in the search set in "quotes", e.g.
+"./SRR_file1.sra ./SRR_file2.sra ./SRR_file3.sra"
+
+Example:
+
+./blastn_vdb -db "./ERR039542.sra ./ERR047215.sra ./ERR039539.sra ./ERR039540.sra" -query nt.test -out test.out
+
+Caveats
+-------
+There are some limitations on the currently available application:
+
+1) Individual SRA data files containing more than 2 billion reads are not yet supported. For a 
+paired-end experiment this is actually a limitation of about 1 billion "spots".
+
+2) Compressed SRA ("cSRA") is not yet fully supported. Currently, only the
+unaligned fraction of reads are searched. Compressed SRA are runs containing
+alignments (e.g., ERR230455). Runs can be checked with "vdb-dump" to report if
+they contain alignment information:
+
+    $ vdb-dump -E ERR230455
+    enumerating the tables of database 'ERR230455'
+    tbl #1: PRIMARY_ALIGNMENT
+    tbl #2: REFERENCE
+    tbl #3: SEQUENCE
+
+3) You may need to prefix "./" to the run name for files in your current
+directory.
+
+4) The blast_formatter is not currently able to read native SRA files, so 
+reformatting of results saved as a blast archive is not yet supported.
+
+Common errors and fixes.
+------------------------
+
+1) Failure to provide relative path to manually downloaded SRR file:
+
+./blastn_vdb -db SRR770754.sra -query srr770754_test.fa -out test.out
+Error: NCBI C++ Exception:
+    "vdb2blast_util.cpp", line 253: Error: ncbi::CVDBBlastUtil::x_MakeSRASeqSrc() 
+    - VDB BlastSeqSrc construction failed: Failed to add any run to VDB runset: unsupported while allocating
+    
+Fix:
+Include relative (e.g., "../" or "./") or absolute (e.g., "/home/user/SRA_BLAST_data/") file path with SRR file