What are the differences between long-read and short-read sequencing?

Basis of differentiation 

Long-read sequencing

Short-read sequencing 

Read length

Generates much longer DNA or RNA fragments, typically spanning a few thousand to several thousand base pairs 

Generates relatively shorter DNA or RNA fragments, typically ranging from 50 to 300 base pairs in length

Input DNA requirements

Medium to high 

Low

Throughput 

Lower throughput capabilities due to longer run times and lower read output 

Higher throughput capabilities due to shorter run times and higher read output  

Unique characteristic 

Has the ability to analyze long stretches of DNA or RNA in a single read

Enables simultaneous sequencing of a large number of short fragments in a single run 

Genome assembly

Facilitates the assembly of complete genomes

Fragmented assemblies make it challenging to reconstruct entire genomes 

Detection of structural variations

Excels at detecting large structural variations

Limited ability to identify complex structural variations, especially large ones

Ability to capture entire genomic regions 

Is able to capture entire genomic regions 

Has limited ability to capture complex genomic structures

Base accuracy

Generally lower due to higher error rates inherent in long-read technologies 

Generally higher due to shorter read lengths and more established error correction methods

Cost-Effectiveness

Higher operating costs due to higher instrument and reagent costs as well as longer run times

More cost-effective due to lower cost per base and higher throughput, but can be expensive for large-scale projects

Advantages

• Can read contiguous stretches
• Can handle complex genomic regions

• Faster
• Cheaper
• Can generate high coverage

Ideal for 

Investigation of complex genomic regions such as structural variants, repetitive regions, and large-scale genomic rearrangements 

Targeting sequencing, transcriptomics, and variant detection