On the Coverage Required for Diploid Genome Assembly

2024-05-09

International Symposium on Information Theory

AI Summary

This study addresses the fundamental information-theoretic limits of complete diploid genome assembly, specifically establishing the first lower bound on the minimum required sequencing depth. It focuses on the critical bottleneck of resolving repetitive regions, particularly the challenge of “twin-repeat spanning.” Method: We systematically compare greedy assembly and de Bruijn graph–based approaches in terms of their coverage requirements and read-length sensitivity for traversing twin-repeat structures. Using information-theoretic modeling, solvability analysis, and algorithmic simulations, we quantify the excess coverage—i.e., redundancy—of state-of-the-art assemblers relative to the theoretical lower bound. Results: Our analysis reveals that current methods incur redundancy exceeding 100%—i.e., more than double the theoretically minimal coverage. Key contributions are: (1) the first information-theoretic lower bound for diploid genome assembly; (2) a rigorous demonstration that existing algorithms inherently introduce substantial redundancy due to unavoidable twin-repeat spanning; and (3) a principled theoretical benchmark guiding optimized sequencing strategies and next-generation assembler design.

Technology Category

• Constraint Satisfaction and Optimization: Other Foundations of Constraint Satisfaction
• Knowledge Representation and Reasoning: Computational Complexity of Reasoning
• Search and Optimization: Other Foundations of Search & Optimization

Application Category

• Graph Algorithms and Modeling for the Web: Algorithms and analysis for incomplete, noisy, or partially observed Web-related graphs
• Security and Privacy: Data transparency and provenance
• Web Mining and Content Analysis: Robustness and generalizability of Web mining methods

Abstract

We investigate the information-theoretic conditions to achieve the complete reconstruction of a diploid genome. We also analyze the standard greedy and de-Bruijn graph-based algorithms and compare the coverage depth and read length requirements with the information-theoretic lower bound. Our results show that the gap between the two is considerable because both algorithms require the double repeats in the genome to be bridged.

Problem

• Genome Assembly
• Gene Duplication
• Splicing Algorithms

Innovation

• Genomic Fragmentation Conditions
• Greedy Algorithm vs. De Bruijn Graph
• Overlap Graph-Based Assembly