Coded Shotgun Sequencing

TL;DR

This paper characterizes the capacity of a coded shotgun sequencing channel, showing that coding significantly reduces the number of reads needed for reliable DNA sequence reconstruction compared to the uncoded case.

Contribution

It provides an exact capacity characterization for coded shotgun sequencing, demonstrating improved efficiency in DNA reconstruction with coding strategies.

Findings

Coded sequencing requires fewer reads than uncoded for reliable reconstruction.

Capacity approaches 1 with O(n/log n) reads of length > log n.

Uncoded case needs O(n) reads of length > 2 log n.

Abstract

Most DNA sequencing technologies are based on the shotgun paradigm: many short reads are obtained from random unknown locations in the DNA sequence. A fundamental question, studied in arXiv:1203.6233, is what read length and coverage depth (i.e., the total number of reads) are needed to guarantee reliable sequence reconstruction. Motivated by DNA-based storage, we study the coded version of this problem;i.e., the scenario where the DNA molecule being sequenced is a codeword from a predefined codebook. Our main result is an exact characterization of the capacity of the resulting shotgun sequencing channel as a function of the read length and coverage depth. In particular, our results imply that, while in the uncoded case, $O(n)$ reads of length greater than $2\log{n}$ are needed for reliable reconstruction of a length-$n$ binary sequence, in the coded case, only $O(n/\log{n})$ reads of length greater than $\log{n}$ are needed for the capacity to be arbitrarily close to $1$.