@kuketzblog Hätte ich gerne. Aber wie so viele andere habe auch ich meine Unterlagen nicht rechtzeitig erhalten, obwohl ich sie schon im Dezember beantragt hatte.

“In a large study published in September 2022 ..researchers developed a tool that’s essentially a library of every conceivable change to the N-protein over time. They used deep mutational scanning to predict how each of those changes would affect the ability of 17 antibodies used in 11 commercially available rapid tests to latch onto the virus… can cross-reference changes in each new variant of the virus to quickly assess whether a given test will still work. “

cell.com/cell/fulltext/S0092-8

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Our new #git #cheatsheet is ready for use, thanks to @SciCompAalto: aaltoscicomp.github.io/cheatsh

It's designed for beginners/intermediates to introduce things slowly, recognizing that most use is simple, and grouping advanced uses together how they are used. It'll be used in our workshop next week. #RSEng #HPC #teaching

@yokofakun For 2FA I invested in a pair of hardware security keys recently and I'm very happy with it. No more looking up codes in an app, just press the button on the key instead.

For all the folks starting their #PhD (or their master thesis) today - a reminder why your PhD advisor can solve a problem so "easily" ...

#astrodon #academia #AcademiChatter #research

My favorite paper that I've read this year — a look at how confusion between inferential uncertainty and outcome variability creates all sorts of problems — is now out in PNAS.

Here's the paper: pnas.org/doi/abs/10.1073/pnas.

Here's the thread I wrote about the preprint last April: fediscience.org/@ct_bergstrom/

Optimizing #RShiny applications with webR is a game-changer 🤯 By leveraging browser-based computation, we witness a significant reduction in server load and enhanced responsiveness.

Dive deeper into the technical insights: appsilon.com/bringing-webr-int

#webR #RStats

alright #rstats , no cheating -- without running it beforehand, what would you expect this code to do?

add <- function(a, b) {
a + b
} / 2

add(2, 4)

In new study, we develop rigorous method to jointly analyze deep mutational scanning of different protein homologs or conditions

We use it to identify mutations w effects on spike-mediated viral entry that differ by >1,000-fold among #SARSCoV2 strains.

biorxiv.org/content/10.1101/20

Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs

Deep mutational scanning (DMS) is a high-throughput experimental technique that measures the effects of thousands of mutations to a protein. These experiments can be performed on multiple homologs of a protein or on the same protein selected under multiple conditions. It is often of biological interest to identify mutations with shifted effects across homologs or conditions. However, it is challenging to determine if observed shifts arise from biological signal or experimental noise. Here, we describe a method for jointly inferring mutational effects across multiple DMS experiments while also identifying mutations that have shifted in their effects among experiments. A key aspect of our method is to regularize the inferred shifts, so that they are nonzero only when strongly supported by the data. We apply this method to DMS experiments that measure how mutations to spike proteins from SARS-CoV-2 variants (Delta, Omicron BA.1, and Omicron BA.2) affect cell entry. Most mutational effects are conserved between these spike homologs, but a fraction have markedly shifted. We experimentally validate a subset of the mutations inferred to have shifted effects, and confirm differences of >1,000-fold in the impact of the same mutation on spike-mediated viral infection across spikes from different SARS-CoV-2 variants. Overall, our work establishes a general approach for comparing sets of DMS experiments to identify biologically important shifts in mutational effects. ### Competing Interest Statement J.D.B. is on the scientific advisory boards of Apriori Bio, Aerium Therapuetics, Invivyd, and the Vaccine Company. J.D.B. consults for Pfizer and GSK. J.D.B. and B.D. are inventors on Fred Hutch licensed patents related to the deep mutational scanning of viral proteins.

www.biorxiv.org

Pacybara: Accurate long-read sequencing for barcoded mutagenized allelic libraries.
Our pre-print is now available: biorxiv.org/content/10.1101/20

@fritzroth

Pacybara: Accurate long-read sequencing for barcoded mutagenized allelic libraries

Long read sequencing technologies, an attractive solution for many applications, usually suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some applications, e.g. the sequencing of mutagenized libraries where multiple distinct clones differ by one or few variants, require the use of barcodes or unique molecular identifiers. Unfortunately, not only can sequencing errors interfere with correct barcode identification, but a given barcode sequence may be linked to multiple independent clones within a given library. Here we focus on the target application of sequencing mutagenized libraries in the context of multiplexed assays of variant effects (MAVEs). MAVEs are increasingly used to create comprehensive genotype-phenotype maps that can aid clinical variant interpretation. Many MAVE methods use barcoded mutant libraries and thus require the accurate association of barcode with genotype, e.g. using long-read sequencing. Existing pipelines do not account for inaccurate sequencing or non-unique barcodes. Here, we describe Pacybara, which handles these issues by clustering long reads based on the similarities of (error-prone) barcodes while detecting the association of a single barcode with multiple genotypes. Pacybara also detects recombinant (chimeric) clones and reduces false positive indel calls. In an example application, we show that Pacybara increases the sensitivity of a MAVE-derived missense variant effect map. ### Competing Interest Statement FP is a shareholder and advisor for SeqWell, Constantiam, BioSymetrics, and a shareholder of Ranomics.

www.biorxiv.org

Is it left handed or this some sort of optical illusion? 🧐
---
RT @hajirasouliha
A DNA double helix molecule made of drones! #AGBT23
twitter.com/hajirasouliha/stat

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