Experimental design, preprocessing, normalization and differential expression analysis of small RNA sequencing experiments

Table 1 Comparison of next-generation sequencing technologies^a

Technology	Approach	Approximate sequencing depth	Read length, nt	Paired ends	Accuracy	Individual molecule sequencing	Optimal for sRNA
Illumina (Solexa)	Synthesis	500 M reads/flow cell, 12 Gb/35-nt run	35 to 75	Optional	≥98% to 99%	No	Yes
454	Synthesis	1.6 M reads/flow cell or 500 Mb/run	400	Optional	≥99%	No	No
Helicos	Synthesis	300 to 500 M reads/flow cell	25 to 55	Optional	> 99.995%	Yes	Yes
SMRT	Synthesis	75 K reads/flow cell	1,000	N/A	99.30%	Yes	No
SOLiD	Ligation	2.4 B reads/flow cell or 300 Gb/run	35 to 75	Optional	≥99.94%	No	Yes
Polonator	Ligation	64 to 80 M mappable reads or 2.2.5 Gb/flow cell	13	Mandatory	98%	No	No

^ant, nucleotides; sRNA, small RNA; SMRT, small-molecule, real-time sequencing; SOLid, sequencing by oligonucleotide ligation and detection.