Disclosed are methods and kits for improving global gene expression analysis for a population of RNA molecules derived from a human blood, plasma and/or serum sample. In an embodiment, the method comprises the step of selectively depleting 5′-RNAY4 fragments from the population of RNA molecules or selectively blocking 5′-RNAY4 fragments within the RNA population. The 5′-RNAY4 depleted or 5′-RNAY4 blocked population of RNA can be used in a variety of global gene expression analysis protocols, including next generation sequencing. In a further embodiment, the method comprises selectively depleting or blocking miR-486-5p fragments within the RNA population. The miR-486-5p depleted or miR-486-5p blocked population of RNA can also be used in global gene expression analysis protocols, including next generation sequencing. The kit comprises oligonucleotide probes comprising a nucleotide sequence that is the complement to a nucleotide sequence of the 5′ end of the RNAY4 and/or oligonucleotide probes comprising a nucleotide sequence that is the complement to a nucleotide sequence of miR-486-5p.