The short-read sequencing platforms can be divided into two major
approaches: sequencing by ligation (SBL) and sequencing by syn-
thesis (SBS). SBL depends on the ligation of labeled probes to
DNA strands where the probes encode one or two bases; thus the
binding of labeled probes and DNA could be recorded for
subsequent base reorganization [116]. Among those NGS plat-
forms based on ligation, SOLiD was the most famous one which
used two-base-encoded probes for ligation. Although very high
accuracy could be achieved by SOLiD, those disadvantages such
as short length of reads, underrepresentation of AT-rich region, and
long-lasting runtimes undermined its application [117–119]. In
contrast, the SBS platforms have better performance. In 2004,
Roche developed the first NGS platform: 454 pyrosequencing plat-
form which incorporated single nucleotide into the strand and
detects the bioluminescence signal via charge-coupled device each
cycle [120]. Unfortunately, 454 platform fell into disuse in 2016
because of its low output and high cost as well as its weakness in
sequencing the homopolymer region [121]. In 2010, Thermo
Fisher developed Ion Torrent platform where the length of reads
could reach almost 400 bp. Unlike the other platforms, Ion Torrent
platform detects the H+ions which are produced during dNTP
incorporation by integrating complementary metal-oxide-semicon-
ductor (CMOS) and ion-sensitive field-effect transistor (ISFET)
[122]. Compared to 454 and Ion Torrent platforms which add
single nucleotide in each cycle, Illumina has developed series of
NGS platforms which terminate the elongation in every cycle
[123]. Illumina developed its first SBS platform—Solexa 1G—in
2006 [124]. It was a rememberable event because it made it possi-
ble to acquire gigabyte (Gb) data from a single run. Nowadays
Illumina has dominated the NGS market for several years, and
their products ranged from low-throughput platform (miniSeq)
to very-high-throughput platform (HiSeq). Noteworthy, HiSeq X
NGS platform could produce 1.8 terabytes in a single run with the
cost of only $7 per Gb data [115]. Recently, a new platform called
NovaSeq is announcing $100 per human genome in the future.
With NGS platform, we could perform various types of
sequencing such as whole genome sequencing (WGS), whole
exome sequencing (WES), transcriptome sequencing (RNA-seq)
[125], chromatin immunoprecipitation followed by sequencing
(ChIP-seq) [126, 127], assay for transposase-accessible chromatin
using sequencing (ATAC-seq) [127], DNA methylation sequenc-
ing (methyl-seq) [128], etc. Compared with WGS, WES is always
performed with high coverage because the specific genomic region
for sequencing and this advantage could facilitate the investigation
on tumor subclones during relapse [129]. However, the structure
variations could be efficiently called in WGS but attenuated identi-
fication in WES. RNA-seq was commonly used to quantify theInsights of Acute Lymphoblastic Leukemia with Development of Genomic... 401