I have a question regarding the alignment of RNA-Seq data.
Let us consider the following two strategies:
(1) Genome ALigner to Transcriptome. E.g., use bowtie to align the reads to a fasta file with all transcript sequences - strategy used by several DE software, bitseq, RSem, mmseq, etc.
(2) Splice-aware aligner. E.g., tophat, STAR, etc.
Which is a better approach, (1) or (2) for aligning RNA-Seq data? Probably the (2) approach is more principle but if that's the case what are the hazards/limitations of the first approach. I can think of a trivial case for total RNA since the reads won't ONLY come from the transcriptome but I am more interested in the case of polyA+ type of experiments, where most reads should come from the transcriptome.
I am looking for practical experience with the data as well as any theoretical consideration.