Hi, I am running STAR with my human samples, using GRCh38. However, some of my samples got very low alignment rate. Most of the reads are unmapped: too short. Is there any suggestions on how to deal with this?
I'm not sure but have you check the QC of your data before alignment by FastQC?
You need to check three level of QC :
1- Quality check, removing the bases with Q less than Q20/Q30.
2- Removing the possible adapter contamination.
3- Removing first bases contamination, 5' or even in some samples 3'. ( mostly 10-15 bases would be enough).
Maybe trying other aligner also worth but it will not changing too much.
If you have successfully done the above issues, you need to consider other issues.