Data storage in DNA is developing as a possible solution for archival digital data. Recently, to further increase the potential capacity of DNA-based data storage systems, the combinatorial composite DNA synthesis method was suggested. This approach extends the DNA alphabet by harnessing short DNA fragment reagents, known as shortmers. The shortmers are building blocks of the alphabet symbols, each consisting of a fixed number of shortmers. Thus, when information is read, it is possible that one of the shortmers that forms part of the composition of a symbol is missing and therefore the symbol cannot be determined. In this paper, we model this type of error as a type of asymmetric error and propose code constructions that can correct such errors in this setup. We also provide a lower bound on the redundancy of such error-correcting codes and give an explicit encoder and decoder for our construction. Our suggested error model is also supported by an analysis of data from actual experiments that produced DNA according to the combinatorial scheme. Lastly, we also provide a statistical evaluation of the probability of observing such error events, as a function of read depth.

Solid tumors are characterized by complex interactions between the tumor, the immune system and the microenvironment. These interactions and intra-tumor variations have both diagnostic and prognostic significance and implications. However, quantifying the underlying processes in patient samples requires expensive and complicated molecular experiments. In contrast, H&E staining is typically performed as part of the routine standard process, and is very cheap. Here we present HIPI (H&E Image Interpretation and Protein Expression Inference) for predicting cell marker expression from tumor H&E images. We process paired H&E and CyCIF images taken from serial sections of colorectal cancers to train our model. We show that our model accurately predicts the spatial distribution of several important cell markers, on both held-out tumor regions as well as new tumor samples taken from different patients. Moreover, using only the tissue image morphology, HIPI is able to colocalize the interactions between different cell types, further demonstrating its potential clinical significance.

Using synthetic DNA for data storage and for physical information encoding in labeling, tracing, and authentication applications is becoming more feasible as synthesis and reading technologies are improving. DNA in data storage applications has several advantages such as very high physical density and robustness. Some of the new synthesis technologies lead to repetition noise, consisting of sticky insertions and deletions in the resulting messages. In this paper, we address reconstruction algorithms for multiple trace communication channels with repetition (sticky insertion and deletion) noise. We prove correctness and analyze failure rates, both analytically and on simulated data. We identify a failure mechanism related to alternating stretches in the design sequence that leads to a potential bias in the data derived from reads (traces) and used for reconstruction. To minimize this effect we introduce alternating length limited codes (ALL codes) and analyze some of their properties.

Synthetic DNA is an attractive alternative for data storage media due to its high information density, low energy usage, and exceptional robustness. Enzymatic DNA synthesis was recently introduced to allow cost effective synthesis of longer DNA molecules for data storage. This method is characterized by stutter errors which are sticky insertions so that every base in the designed sequence may be synthesized more than once. In this work, we study the problem of reconstructing the original sequence from a set of noisy reads originating from the stuttering enzymatic synthesis. We present different reconstruction algorithms and analyze their expected success probability and error rate for three different scenarios that depend on the information which is known about the stutter errors. We evaluate algorithmic performance analytically as well as by using simulations. We are especially interested in characterizing the performance as a function of the read depth. Our findings can be used to evaluate the trade-offs between synthesis quality indicators and the sequencing depth required for reconstruction with high probability. In principle, the probability of reconstruction failure exponentially decays with the sequencing depth, as demonstrated in the study. We also analyze the use of error-correcting codes to improve the error performance.

MOTIVATION: Recent years have seen a growing number and an expanding scope of studies using synthetic oligo libraries for a range of applications in synthetic biology. As experiments are growing by numbers and complexity, analysis tools can facilitate quality control and support better assessment and inference. RESULTS: We present a novel analysis tool, called SOLQC, which enables fast and comprehensive analysis of synthetic oligo libraries, based on NGS analysis performed by the user. SOLQC provides statistical information such as the distribution of variant representation, different error rates and their dependence on sequence or library properties. SOLQC produces graphical reports from the analysis, in a flexible format. We demonstrate SOLQC by analyzing literature libraries. We also discuss the potential benefits and relevance of the different components of the analysis. AVAILABILITY AND IMPLEMENTATION: SOLQC is a free software for non-commercial use, available at https://app.gitbook.com/@yoav-orlev/s/solqc/. For commercial use please contact the authors. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.