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Golan, S.

Publications and source records attributed to Golan, S..

2 recordsLinked to original sources
bioRxiv2024

Generating low-density minimizers

Minimizers is the most popular k-mer selection scheme in algorithms and data structures analyzing high-throughput sequencing (HTS) data. In a minimizers scheme, the smallest k-mer by some predefined order is selected as the representative of a sequence window containing w consecutive k-mers, which results in overlapping windows often selecting the same k-mer. Minimizers that achieve the lowest frequency of selected k-mers over a random DNA sequence, termed the expected density, are desired for improved performance of HTS analyses. Yet, no method to date exists to generate minimizers that achieve minimum expected density. Moreover, for k and w values used by common HTS algorithms and data structures there is a gap between the densities achieved by existing selection schemes and a recent theoretical lower bound. Here, we present GreedyMini, a toolkit of methods to generate minimizers with low expected or particular density, to improve minimizers, to extend minimizers to larger alphabets, k, and w, and to measure the expected density of a given minimizer efficiently. We demonstrate over various combinations of k and w values, including those of popular HTS methods, that GreedyMini can generate DNA minimizers that achieve expected densities very close to the lower bound, and both expected and particular densities much lower compared to existing selection schemes. Additionally, we show that the k-mer rank-retrieval time by GreedyMini is comparable to that of common k-mer hash functions. We expect GreedyMini to improve the performance of many HTS algorithms and data structures and advance the research of k-mer selection schemes.

bioinformatics↗
bioRxiv2024

Anomaly detection for high-content image-based phenotypic cell profiling

High-content image-based phenotypic profiling combines automated microscopy and analysis to identify phenotypic alterations in cell morphology and provide insight into the cells physiological state. Classical representations of the phenotypic profile can not capture the full underlying complexity in cell organization, while recent weakly machine-learning based representation-learning methods are hard to biologically interpret. We used the abundance of control wells to learn the in-distribution of control experiments and use it to formulate a self-supervised reconstruction anomaly-based representation that encodes the intricate morphological inter-feature dependencies while preserving the representation interpretability. The performance of our anomaly-based representations was evaluated for downstream tasks with respect to two classical representations across four public Cell Painting datasets. Anomaly-based representations improved reproducibility, Mechanism of Action classification, and complemented classical representations. Unsupervised explainability of autoencoder-based anomalies identified specific inter-feature dependencies causing anomalies. The general concept of anomaly-based representations can be adapted to other applications in cell biology.

bioinformatics↗