Biology subjects

Lior Pachter

Publications and source records attributed to Lior Pachter.

6 recordsLinked to original sources

bioRxiv2016

Zika infection of neural progenitor cells perturbs transcription in neurodevelopmental pathways

BackgroundA recent study of the gene expression patterns of Zika virus (ZIKV) infected human neural progenitor cells (hNPCs) revealed transcriptional dysregulation and identified cell-cycle-related pathways that are affected by infection. However deeper exploration of the information present in the RNA-Seq data can be used to further elucidate the manner in which Zika infection of hNPCs affects the transcriptome, refining pathway predictions and revealing isoform-specific dynamics.\n\nMethodology/Principal FindingsWe analyzed data published by Tang et al. using state-of-the-art tools for transcriptome analysis. By accounting for the experimental design and estimation of technical and inferential variance we were able to pinpoint Zika infection affected pathways that highlight Zikas neural tropism. The examination of differential genes reveals cases of isoform divergence.\n\nConclusions/SignificanceTranscriptome analysis of Zika infected hNPCs has the potential to identify the molecular signatures of Zika infected neural cells. These signatures may be useful for diagnostics and for the resolution of infection pathways that can be used to harvest specific targets for further study.

Bioinformatics↗

bioRxiv2016

Prober: A general toolkit for analyzing sequencing-based ‘toeprinting’ assays

A number of high-throughput transcriptase drop-off assays have recently been developed to probe post-transcriptional dynamics of RNA-protein interaction, RNA structure, and post-transcriptional modifications. Although these assays survey a diverse set of epitranscriptomic marks, they share methodological similarities and as such their interpretation is predicated on addressing similar computational challenges. Among these, a key question is how to learn isoform-specific chemical modification profiles in the face of complex read multi-mapping. In this paper, we propose PROBer, the first rigorous statistical model to handle these challenges for a general set of sequencing-based toeprinting assays.

Genomics↗

bioRxiv2016

Differential analysis of RNA-Seq incorporating quantification uncertainty

We describe a novel method for the differential analysis of RNA-Seq data that utilizes bootstrapping in conjunction with response error linear modeling to decouple biological variance from inferential variance. The method is implemented in an interactive shiny app called sleuth that utilizes kallisto quantifications and bootstraps for fast and accurate analysis of RNA-Seq experiments.

Bioinformatics↗

bioRxiv2016

The Lair: A resource for exploratory analysis of published RNA-Seq data

Increased emphasis on reproducibility of published research in the last few years has led to the large-scale archiving of sequencing data. While this data can, in theory, be used to reproduce results in papers, it is typically not easily usable in practice. We introduce a series of tools for processing and analyzing RNA-Seq data in the Short Read Archive, that together have allowed us to build an easily extendable resource for analysis of data underlying published papers. Our system makes the exploration of data easily accessible and usable without technical expertise. Our database and associated tools can be accessed at The Lair: http://pachterlab.github.io/lair

Bioinformatics↗

bioRxiv2016

Shannon: An Information-Optimal de Novo RNA-Seq Assembler

De novo assembly of short RNA-Seq reads into transcripts is challenging due to sequence similarities in transcriptomes arising from gene duplications and alternative splicing of transcripts. We present Shannon, an RNA-Seq assembler with an optimality guarantee derived from principles of information theory: Shannon reconstructs nearly all information-theoretically reconstructable transcripts. Shannon is based on a theory we develop for de novo RNA-Seq assembly that reveals differing abundances among transcripts to be the key, rather than the barrier, to effective assembly. The assembly problem is formulated as a sparsest-flow problem on a transcript graph, and the heart of Shannon is a novel iterative flow-decomposition algorithm. This algorithm provably solves the information-theoretically reconstructable instances in linear-time even though the general sparsest-flow problem is NP-hard. Shannon also incorporates several additional new algorithmic advances: a new error-correction algorithm based on successive cancelation, a multi-bridging algorithm that carefully utilizes read information in the k-mer de Bruijn graph, and an approximate graph partitioning algorithm to split the transcriptome de Bruijn graph into smaller components. In tests on large RNA-Seq datasets, Shannon obtains significant increases in sensitivity along with improvements in specificity in comparison to state-of-the-art assemblers.

Genomics↗

bioRxiv2016

Fast and accurate single-cell RNA-Seq analysis by clustering of transcript-compatibility counts

Current approaches to single-cell transcriptomic analysis are computationally intensive and require assay-specific modeling which limit their scope and generality. We propose a novel method that departs from standard analysis pipelines, comparing and clustering cells based not on their transcript or gene quantifications but on their transcript-compatibility read counts. In re-analysis of two landmark yet disparate single-cell RNA-Seq datasets, we show that our method is up to two orders of magnitude faster than previous approaches, provides accurate and in some cases improved results, and is directly applicable to data from a wide variety of assays.

Genomics↗