bioRxiv Science⌕ Search

bioRxiv · 10.1101/301242

Learning and Imputation for Mass-spec Bias Reduction (LIMBR)

Abstract

MotivationDecreasing costs are making it feasible to perform time series proteomics and genomics experiments with more replicates and higher resolution than ever before. With more replicates and time points, proteome and genome-wide patterns of expression are more readily discernible. These larger experiments require more batches exacerbating batch effects and increasing the number of bias trends. In the case of proteomics, where methods frequently result in missing data this increasing scale is also decreasing the number of peptides observed in all samples. The sources of batch effects and missing data are incompletely understood necessitating novel techniques.\n\nResultsHere we show that by exploiting the structure of time series experiments, it is possible to accurately and reproducibly model and remove batch effects. We implement Learning and Imputation for Mass-spec Bias Reduction (LIMBR) software, which builds on previous block based models of batch effects and includes features specific to time series and circadian studies. To aid in the analysis of time series proteomics experiments, which are often plagued with missing data points, we also integrate an imputation system. By building LIMBR for imputation and time series tailored bias modeling into one straightforward software package, we expect that the quality and ease of large-scale proteomics and genomics time series experiments will be significantly increased.\n\nContactalexander.m.crowell@gmail.com, jay.c.dunlap@dartmouth.edu

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Crowell, A. M., Greene, C. S., Loros, J. J., Dunlap, J. C.. 2018-04-14. Learning and Imputation for Mass-spec Bias Reduction (LIMBR). https://doi.org/10.1101/301242

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Cross-modal transfer enables zero-shot prediction of drug responses across cell types

Genetic perturbation responses capture the functional consequences of gene-level interventions, providing functional information for drug-response prediction beyond baseline gene expression. Within the same cellular context, genetic and chemical perturbations engage shared regulatory networks, providing a biological basis for transferring response information between perturbation modalities. Here we introduce GRAFT, a framework that combines genetic-to-chemical transfer with cross-context prediction to infer drug-induced transcriptional responses without drug measurements in the target context. Across benchmarked LINCS and external contexts, GRAFT improved response correlation, directional agreement and magnitude reconstruction over competing methods, particularly for drugs with context-dependent responses. GRAFT-Adapt further refines predictions of unmeasured responses using a small number of drug measurements from the target context. GRAFT-Atlas spans 13 cellular contexts and 7,856 drug catalog entries, comprising 102,128 predictions for drug-context combinations. The atlas captured recognizable pharmacological neighborhoods, shared functional programs, context-dependent transcriptional changes and structural-functional associations supported by molecular docking. Across ten iPSC lines from distinct donors, GRAFT identified candidate inter-donor differences, with functional support for selected candidates from measured genetic perturbation responses. Together, GRAFT enables perturbation-informed prediction and comparison of drug responses across cellular contexts.

bioinformatics↗

Pycea: a scverse toolkit for single-cell lineage tracing analysis

Lineage tracing enables reconstruction of cellular histories in development, regeneration, and disease, but integrating lineage data into single-cell analysis workflows remains challenging. We introduce Pycea, a Python toolkit for lineage analysis and visualization, and TreeData, an extension of AnnData that stores lineage trees alongside cellular measurements. TreeData is compatible with Scanpy and other scverse tools, enabling integrated analysis without converting between formats. Pycea provides scalable methods for tree visualization, clade identification, distance comparisons, ancestral state inference, and lineage statistics. This software is open source and available at https://github.com/YosefLab/pycea.

bioinformatics↗

Transcript quantification using context-aware MAPQ modeling

Long-read RNA-sequencing enables accurate transcript-level quantification, but prior static filtering of MAPping Quality (MAPQ) can ignore transcriptome-intrinsic ambiguity, and discarding reads on this basis distorts abundance estimates. We present CALMeR (Context-Aware Long-read MAPQ-based Rescuer), which conditions MAPQ filtering on transcript properties rather than a fixed cutoff. CALMeR fits a zero-one inflated beta regression on various transcript and read-level features to model the expected MAPQ distribution for each alignment. Reads whose MAPQ fits this context, such as low-MAPQ reads from multi-isoform genes and paralog families are retained; reads with anomalously low MAPQ are removed as likely artifacts. Retained reads can be summed per transcript or passed to any downstream quantifier. Compared with a MAPQ [≥] 1 filter and expectation-maximization-based transcript quantification methods, CALMeR recovers more spike-in transcripts and better matches known spike-in concentrations. CALMeR is available at https://github.com/sparthib/CALMeR.

bioinformatics↗