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We present a framework for the design of optimal assembly algorithms for shotgun sequencing under the criterion of complete reconstruction. We derive a lower bound on the read length and the coverage depth required for reconstruction in…

Genomics · Quantitative Biology 2013-02-20 Guy Bresler , Ma'ayan Bresler , David Tse

DNA sequencing is the basic workhorse of modern day biology and medicine. Shotgun sequencing is the dominant technique used: many randomly located short fragments called reads are extracted from the DNA sequence, and these reads are…

Information Theory · Computer Science 2013-02-15 Abolfazl Motahari , Guy Bresler , David Tse

We establish the fundamental limits of DNA shotgun sequencing under noisy reads. We show a surprising result: for the i.i.d. DNA model, noisy reads are as good as noiseless reads, provided that the noise level is below a certain threshold…

Information Theory · Computer Science 2013-04-11 Abolfazl Motahari , Kannan Ramchandran , David Tse , Nan Ma

The prevalent technique for DNA sequencing consists of two main steps: shotgun sequencing, where many randomly located fragments, called reads, are extracted from the overall sequence, followed by an assembly algorithm that aims to…

Genomics · Quantitative Biology 2016-01-28 Shirshendu Ganguly , Elchanan Mossel , Miklos Z. Racz

Genome sequencing is the basis for many modern biological and medicinal studies. With recent technological advances, metagenomics has become a problem of interest. This problem entails the analysis and reconstruction of multiple DNA…

Probability · Mathematics 2022-01-14 Marlee Herring

High read depth can be used to assemble short sequence repeats. The existing genome assemblers fail in repetitive regions of longer than average read. I propose a new algorithm for a DNA assembly which uses the relative frequency of reads…

Genomics · Quantitative Biology 2015-01-08 Robert M. Nowak

In this paper, fundamental limits in sequencing of a set of closely related DNA molecules are addressed. This problem is called pooled-DNA sequencing which encompasses many interesting problems such as haplotype phasing, metageomics, and…

Information Theory · Computer Science 2016-04-20 Amir Najafi , Damoun Nashta-ali , Seyed Abolfazl Motahari , Mehrdad Khani , Babak H. Khalaj , Hamid R. Rabiee

While most current high-throughput DNA sequencing technologies generate short reads with low error rates, emerging sequencing technologies generate long reads with high error rates. A basic question of interest is the tradeoff between read…

Information Theory · Computer Science 2015-01-27 Ilan Shomorony , Thomas Courtade , David Tse

The repeat content and heterozygosity rate of a target genome are important factors in determining the feasibility of achieving a complete telomere-to-telomere assembly. The mathematical relationship between the required coverage and read…

Information Theory · Computer Science 2025-04-08 Daanish Mahajan , Chirag Jain , Navin Kashyap

We obtain an information theoretic criterion for the feasibility of assembling diffraction signals from noisy tomographs when the positions of the tomographs within the signal are unknown. For shot-noise limited data, the minimum number of…

Computational Physics · Physics 2007-09-26 Veit Elser

The shotgun sequencing process involves fragmenting a long DNA sequence (input string) into numerous shorter, unordered, and overlapping segments (referred to as \emph{reads}). The reads are sequenced, and later aligned to reconstruct the…

Information Theory · Computer Science 2025-09-26 Mohammed Ihsan Ali , Hrishi Narayanan , Prasad Krishnan

De novo genome assembly is challenging in highly repetitive regions; however, reference-guided assemblers often suffer from bias. We propose a framework for pangenome-guided sequence assembly, which can resolve short-read data in complex…

Quantum Physics · Physics 2026-02-11 Josh Cudby , James Bonfield , Chenxi Zhou , Richard Durbin , Sergii Strelchuk

Over the past two decades, a series of works have aimed at studying the problem of genome assembly: the process of reconstructing a genome from sequence reads. An early formulation of the genome assembly problem showed that genome…

Genomics · Quantitative Biology 2013-12-30 Henry Lin

Deep shotgun sequencing and analysis of genomes, transcriptomes, amplified single-cell genomes, and metagenomes has enabled investigation of a wide range of organisms and ecosystems. However, sampling variation in short-read data sets and…

Genomics · Quantitative Biology 2012-05-22 C. Titus Brown , Adina Howe , Qingpeng Zhang , Alexis B. Pyrkosz , Timothy H. Brom

De novo assembly is the process of reconstructing the genome sequence of an organism from sequencing reads. Genome sequences are essential to biology, and assembly has been a central problem in bioinformatics for four decades. Until…

Genomics · Quantitative Biology 2023-08-16 Heng Li , Richard Durbin

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…

Information Theory · Computer Science 2022-02-09 Aditya Narayan Ravi , Alireza Vahid , Ilan Shomorony

Genome assembly using high throughput data with short reads, arguably, remains an unresolvable task in repetitive genomes, since when the length of a repeat exceeds the read length, it becomes difficult to unambiguously connect the flanking…

Quantitative Methods · Quantitative Biology 2013-07-31 Viraj Deshpande , Eric DK Fung , Son Pham , Vineet Bafna

We consider the problem of detecting the overlap between a pair of short fragments sampled in random locations from an exponentially longer sequence, via their possibly noisy reads. We consider a noiseless setting, in which the reads are…

Information Theory · Computer Science 2025-02-20 Nir Luria , Nir Weinberger

(An updated version of this manuscript has been accepted to Scientific Reports in 2016, please refer to http://www.nature.com/articles/srep31900) The highly anticipated transition from next generation sequencing (NGS) to third generation…

Genomics · Quantitative Biology 2016-09-06 Chengxi Ye , Chris Hill , Shigang Wu , Jue Ruan , Zhanshan , Ma

The de novo assembly of large, complex genomes is a significant challenge with currently available DNA sequencing technology. While many de novo assembly software packages are available, comparatively little attention has been paid to…

Genomics · Quantitative Biology 2013-07-31 Jared T. Simpson
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