Biology subjects

Heckel, R.

Publications and source records attributed to Heckel, R..

6 recordsLinked to original sources

bioRxiv2025

Comparison of state-of-the-art error-correction coding for sequence-based DNA data storage

A wide range of codecs with vastly different error-correction approaches have been proposed and implemented for DNA data storage to date. However, while many codecs claim to provide superior performance, no studies have systematically benchmarked codec implementations to establish the current state-of-the-art in DNA data storage. In this study, we use standardized error scenarios - both in silico and in vitro - to compare the performance of six representative codecs from the literature. We find synthetic benchmarks commonly used in literature to be unsuitable indicators of codec performance, as our data shows that common experimental benchmarks fail to differentiate codecs under standardized conditions. Instead, we implement a comprehensive benchmark covering the major experimental parameters to assess codec performance under realistic DNA data storage conditions, while establishing important baselines for future codec development. Verifying our results with fair and standardized experiments, we demonstrate data storage at 43 EB g-1 using synthesis by material deposition and 13 EB g-1 using the more error prone electrochemical synthesis, employing only existing codecs from the literature. Besides closing in on the physical limits of DNA data storage, this study thus showcases the maturity of error-correction coding and defines its current state-of-the-art.

bioinformatics↗

bioRxiv2025

ProPicker: Promptable Segmentation for Particle Picking in CryogenicElectron Tomography

Cryogenic electron tomography (cryo-ET) produces detailed 3D images (tomograms) of cellular environments. A key step in cryo-ET data analysis is detecting all instances of a specific particle across tomograms (particle picking). This is a challenging object detection task due to strong noise, artefacts, and the crowded cellular context. Here, we propose ProPicker, a pretrained, promptable 3D segmentation model that enables a flexible and data-efficient particle picking workflow. By specifying a prompt, ProPicker is conditioned to detect a particle of interest and can then be used directly or can be fine-tuned to a particle-specific picker for improved accuracy. Experiments on simulated and real-world tomograms show that, using a single prompt, ProPicker achieves performance close to or on par with state-of-the-art methods while being up to an order of magnitude faster. Moreover, ProPicker can detect particles not seen during training. Fine-tuning ProPicker outperforms state-of-the-art particle-specific pickers if limited training data is available.

bioinformatics↗

bioRxiv2024

Challenges for error-correction coding in DNA data storage: photolithographic synthesis and DNA decay

Efficient error-correction codes are crucial for realizing DNAs potential as a long-lasting, high-density storage medium for digital data. At the same time, new workflows promising low-cost, resilient DNA data storage are challenging their design and error-correcting capabilities. This study characterizes the errors and biases in two new additions to the state-of-the-art workflow in DNA data storage: photolithographic synthesis and DNA decay. Photolithographic synthesis offers low-cost, scalable oligonucleotide synthesis but suffers from high error rates, necessitating sophisticated error-correction schemes, for example codes introducing within-sequence redundancy combined with clustering and alignment techniques for retrieval. On the other hand, the decoding of oligo fragments after DNA decay promises unprecedented storage densities, but complicates data recovery by requiring the reassembly of full-length sequences or the use of partial sequences for decoding. Our analysis provides a detailed account of the error patterns and biases present in photolithographic synthesis and DNA decay, and identifies considerable bias stemming from sequencing workflows. We implement our findings into a digital twin of the two workflows, offering a tool for developing error-correction codes and providing benchmarks for the evaluation of codec performance.

biochemistry↗

bioRxiv2023

A digital twin for DNA data storage based on comprehensive quantification of errors and biases

Archiving data in synthetic DNA offers unprecedented storage density and longevity. Handling and storage introduce errors and biases into DNA-based storage systems, necessitating the use of Error Correction Coding (ECC) which comes at the cost of added redundancy. However, insufficient data on these errors and biases, as well as a lack of modelling tools, limit data-driven ECC development and experimental design. In this study, we present a comprehensive characterisation of the error sources and biases present in the most common DNA data storage workflows, including commercial DNA synthesis, PCR, decay by accelerated aging, and sequencing-by-synthesis. Using the data from 40 sequencing experiments, we build a digital twin of the DNA data storage process, capable of simulating state-of-the-art workflows and reproducing their experimental results. We showcase the digital twins ability to replace experiments and rationalize the design of redundancy in two case studies, highlighting opportunities for tangible cost savings and data-driven ECC development.

synthetic biology↗

bioRxiv2022

Information Decay and Enzymatic Information Recovery for DNA Data Storage

Synthetic DNA has been proposed as a storage medium for digital information due to its high theoretical storage density and anticipated long storage horizons. However, under all ambient storage conditions, DNA undergoes a slow chemical decay process resulting in nicked (broken) DNA strands, and the information stored in these strands is no longer readable. In this work we design an enzymatic repair procedure, which is applicable to the DNA pool prior to readout and can partially reverse the damage. Through a chemical understanding of the decay process, an overhang at the 3 end of the damaged site is identified as obstructive to repair via the base excision-repair (BER) mechanism. The obstruction can be removed via the enzyme apurinic/apyrimidinic endonuclease I (APE1), thereby enabling repair of hydrolytically damaged DNA via Bst polymerase and Taq ligase. Simulations of damage and repair reveal the benefit of the enzymatic repair step for DNA data storage, especially when data is stored in DNA at high storage densities (= low physical redundancy) and for long time durations.

synthetic biology↗

bioRxiv2019

Genomic encryption of digital data stored in synthetic DNA

Today, we can read human genomes and store digital data robustly in synthetic DNA. Here we report a strategy to intertwine these two technologies to enable the secure storage of valuable information in synthetic DNA, protected with personalized keys. We show that genetic short tandem repeats (STRs) contain sufficient entropy to generate strong encryption keys, and that only one technology, DNA sequencing, is required to simultaneously read key and data. Using this approach, we experimentally generated 80 bit strong keys from human DNA, and used such a key to encrypt 17kB of digital information stored in synthetic DNA. Finally, the decrypted information was recovered perfectly from a single massively parallel sequencing run.

synthetic biology↗