Heterogeneous distribution of kinesin-streptavidin complexes revealed by mass photometry.

Kinesin-streptavidin complexes are widely used in microtubule-based active-matter studies. The stoichiometry of the complexes is empirically tuned but experimentally challenging to determine. Here, mass photometry measurements reveal heterogenous distributions of kinesin-streptavidin complexes. Our binding model indicates that heterogeneity arises from both the kinesin-streptavidin mixing ratio and the kinesin-biotinylation efficiency.

Heterogeneous distribution of kinesin-streptavidin complexes revealed by Mass Photometry.

Kinesin-streptavidin complexes are widely used in microtubule-based active-matter studies. The stoichiometry of the complexes is empirically tuned but experimentally challenging to determine. Here, mass photometry measurements reveal heterogenous distributions of kinesin-streptavidin complexes. Our binding model indicates that heterogeneity arises from both the kinesin-streptavidin mixing ratio and the kinesin-biotinylation efficiency.

Faster Maximal Exact Matches with Lazy LCP Evaluation.

MONI (Rossi et al., JCB 2022) is a BWT-based compressed index for computing the matching statistics and maximal exact matches (MEMs) of a pattern (usually a DNA read) with respect to a highly repetitive text (usually a database of genomes) using two operations: LF-steps and longest common extension (LCE) queries on a grammar-compressed representation of the text. In practice, most of the operations are constant-time LF-steps but most of the time is spent evaluating LCE queries. In this paper we show how (a variant of) the latter can be evaluated lazily, so as to bound the total time MONI needs to process the pattern in terms of the number of MEMs between the pattern and the text, while maintaining logarithmic latency.

MEM-based pangenome indexing for k-mer queries.

Pangenomes are growing in number and size, thanks to the prevalence of high-quality long-read assemblies. However, current methods for studying sequence composition and conservation within pangenomes have limitations. Methods based on graph pangenomes require a computationally expensive multiple-alignment step, which can leave out some variation. Indexes based on k-mers and de Bruijn graphs are limited to answering questions at a specific substring length k. We present Maximal Exact Match Ordered (MEMO), a pangenome indexing method based on maximal exact matches (MEMs) between sequences. A single MEMO index can handle arbitrary-length queries over pangenomic windows. MEMO enables both queries that test k-mer presence/absence (membership queries) and that count the number of genomes containing k-mers in a window (conservation queries). MEMO's index for a pangenome of 89 human autosomal haplotypes fits in 2.04 GB, 8.8× smaller than a comparable KMC3 index and 11.4× smaller than a PanKmer index. MEMO indexes can be made smaller by sacrificing some counting resolution, with our decile-resolution HPRC index reaching 0.67 GB. MEMO can conduct a conservation query for 31-mers over the human leukocyte antigen locus in 13.89 seconds, 2.5x faster than other approaches. MEMO's small index size, lack of k-mer length dependence, and efficient queries make it a flexible tool for studying and visualizing substring conservation in pangenomes.

Patient Participation in Multidisciplinary High-Risk Surgery Discussions: A Pilot Study.

Objective: Our medical center implemented a multidisciplinary team to improve surgical decision making for high-risk older adults. To make this a patient-centric process, a pilot program included the patient and their family/caregiver(s) in these conversations. Our hypothesis is that multidisciplinary team discussions can improve difficult surgical decision making. Methods: From January to June 2022, we offered patients and their family participation in multidisciplinary discussions at a Veterans Affairs medical center. Semistructured interviews were conducted 1-6 days after the meeting. Interview transcripts were analyzed with qualitative mixed-methods approach. Results: Six patients and caregivers participated in the interviews. They found the discussion helpful for improving their understanding of the surgical decision. Out of these, 50% (3 of 6) of the patients changed their decision regarding the planned operation based on the discussion. Conclusion: Including patients and caregiver(s) in multidisciplinary surgical decision-making discussions resulted in half of the patients changing their surgical plans. This pilot study demonstrated both acceptance and feasibility for all participants.

Augmented Thresholds for MONI.

MONI (Rossi et al., 2022) can store a pangenomic dataset T in small space and later, given a pattern P, quickly find the maximal exact matches (MEMs) of P with respect to T. In this paper we consider its one-pass version (Boucher et al., 2021), whose query times are dominated in our experiments by longest common extension (LCE) queries. We show how a small modification lets us avoid most of these queries which significantly speeds up MONI in practice while only slightly increasing its size.

RLBWT Tricks.

Until recently, most experts would probably have agreed we cannot backwards-step in constant time with a run-length compressed Burrows-Wheeler Transform (RLBWT), since doing so relies on rank queries on sparse bitvectors and those inherit lower bounds from predecessor queries. At ICALP '21, however, Nishimoto and Tabei described a new, simple and constant-time implementation. For a permutation π , it stores an O r -space table - where r is the number of positions i where either i = 0 or π i + 1 ≠ π i + 1 - that enables the computation of successive values of π i by table look-ups and linear scans. Nishimoto and Tabei showed how to increase the number of rows in the table to bound the length of the linear scans such that the query time for computing π i is constant while maintaining O r -space. In this paper we refine Nishimoto and Tabei's approach, including a time-space tradeoff, and experimentally evaluate different implementations demonstrating the practicality of part of their result. We show that even without adding rows to the table, in practice we almost always scan only a few entries during queries. We propose a decomposition scheme of the permutation π corresponding to the LF-mapping that allows an improved compression of the data structure, while limiting the query time. We tested our implementation on real-world genomic datasets and found that without compression of the table, backward-stepping is drastically faster than with sparse bitvector implementations but, unfortunately, also uses drastically more space. After compression, backward-stepping is competitive both in time and space with the best existing implementations.