3.3CCOct 12, 2020
Trace Reconstruction Problems in Computational BiologyVinnu Bhardwaj, Pavel A. Pevzner, Cyrus Rashtchian et al.
The problem of reconstructing a string from its error-prone copies, the trace reconstruction problem, was introduced by Vladimir Levenshtein two decades ago. While there has been considerable theoretical work on trace reconstruction, practical solutions have only recently started to emerge in the context of two rapidly developing research areas: immunogenomics and DNA data storage. In immunogenomics, traces correspond to mutated copies of genes, with mutations generated naturally by the adaptive immune system. In DNA data storage, traces correspond to noisy copies of DNA molecules that encode digital data, with errors being artifacts of the data retrieval process. In this paper, we introduce several new trace generation models and open questions relevant to trace reconstruction for immunogenomics and DNA data storage, survey theoretical results on trace reconstruction, and highlight their connections to computational biology. Throughout, we discuss the applicability and shortcomings of known solutions and suggest future research directions.
Single-Molecule Protein Identification by Sub-Nanopore SensorsMikhail Kolmogorov, Eamonn Kennedy, Zhuxin Dong et al.
Recent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top-down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore technology is exquisitely sensitive to single intact molecules, but it has only been successfully applied to DNA sequencing, so far. Here, we explore the potential of sub-nanopores for single-molecule protein identification (SMPI) and describe an algorithm for identification of the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. The analysis of identification p-values suggests that the current technology is already sufficient for matching nanospectra against small protein databases, e.g., protein identification in bacterial proteomes.