118 research outputs found
Decon2LS: An open-source software package for automated processing and visualization of high resolution mass spectrometry data
Abstract
Background
Data generated from liquid chromatography coupled to high-resolution mass spectrometry (LC-MS)-based studies of a biological sample can contain large amounts of biologically significant information in the form of proteins, peptides, and metabolites. Interpreting this data involves inferring the masses and abundances of biomolecules injected into the instrument. Because of the inherent complexity of mass spectral patterns produced by these biomolecules, the analysis is significantly enhanced by using visualization capabilities to inspect and confirm results. In this paper we describe Decon2LS, an open-source software package for automated processing and visualization of high-resolution MS data. Drawing extensively on algorithms developed over the last ten years for ICR2LS, Decon2LS packages the algorithms as a rich set of modular, reusable processing classes for performing diverse functions such as reading raw data, routine peak finding, theoretical isotope distribution modelling, and deisotoping. Because the source code is openly available, these functionalities can now be used to build derivative applications in relatively fast manner. In addition, Decon2LS provides an extensive set of visualization tools, such as high performance chart controls.
Results
With a variety of options that include peak processing, deisotoping, isotope composition, etc, Decon2LS supports processing of multiple raw data formats. Deisotoping can be performed on an individual scan, an individual dataset, or on multiple datasets using batch processing. Other processing options include creating a two dimensional view of mass and liquid chromatography (LC) elution time features, generating spectrum files for tandem MS data, creating total intensity chromatograms, and visualizing theoretical peptide profiles. Application of Decon2LS to deisotope different datasets obtained across different instruments yielded a high number of features that can be used to identify and quantify peptides in the biological sample.
Conclusion
Decon2LS is an efficient software package for discovering and visualizing features in proteomics studies that require automated interpretation of mass spectra. Besides being easy to use, fast, and reliable, Decon2LS is also open-source, which allows developers in the proteomics and bioinformatics communities to reuse and refine the algorithms to meet individual needs.
Decon2LS source code, installer, and tutorials may be downloaded free of charge at
http://http:/ncrr.pnl.gov/software/
State-of-the-art Speech Recognition With Sequence-to-Sequence Models
Attention-based encoder-decoder architectures such as Listen, Attend, and
Spell (LAS), subsume the acoustic, pronunciation and language model components
of a traditional automatic speech recognition (ASR) system into a single neural
network. In previous work, we have shown that such architectures are comparable
to state-of-theart ASR systems on dictation tasks, but it was not clear if such
architectures would be practical for more challenging tasks such as voice
search. In this work, we explore a variety of structural and optimization
improvements to our LAS model which significantly improve performance. On the
structural side, we show that word piece models can be used instead of
graphemes. We also introduce a multi-head attention architecture, which offers
improvements over the commonly-used single-head attention. On the optimization
side, we explore synchronous training, scheduled sampling, label smoothing, and
minimum word error rate optimization, which are all shown to improve accuracy.
We present results with a unidirectional LSTM encoder for streaming
recognition. On a 12, 500 hour voice search task, we find that the proposed
changes improve the WER from 9.2% to 5.6%, while the best conventional system
achieves 6.7%; on a dictation task our model achieves a WER of 4.1% compared to
5% for the conventional system.Comment: ICASSP camera-ready versio
Identification of a Putative Protein Profile Associated with Tamoxifen Therapy Resistance in Breast Cancer
Identification of a Putative Protein Profile Associated with Tamoxifen Therapy Resistance in Breast Cancer
Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells
Augment to prevent: short-text data augmentation in deep learning for hate-speech classification
Identification of a putative protein-profile associating with tamoxifen therapy-resistance in breast cancer
Tamoxifen-resistance is a major cause of death in patients with recurrent breast cancer. Current clinical parameters can correctly predict therapy response in only half of the treated patients. Identification of proteins that associate with tamoxifen-resistance is a first step towards better response prediction and tailored treatment of patients.
In the present study we aimed to identify putative protein biomarkers indicative of tamoxifen therapy-resistance in breast cancer, using nanoLC-FTICR MS. Comparative proteome analysis was performed on ~5,500 pooled tumor cells obtained through laser capture microdissection from two independently processed data sets (n=24 and n=27) of tamoxifen therapy-sensitive and -resistant tumors. Peptide and protein identifications were acquired by matching mass and elution time features to information in previously generated accurate mass and time tag reference data bases.
A total of 17,263 unique peptides were identified that corresponded to 2,556 non-redundant proteins identified with >=2 peptides. From this total, 1,713 protein
Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Translation
Using sample-matched transcriptomics and proteomics measurements it is now possible to begin to understand the impact of post-transcriptional regulatory programs in Enterobacteria. In bacteria post-transcriptional regulation is mediated by relatively few identified RNA-binding protein factors including CsrA, Hfq and SmpB. A mutation in any one of these three genes, csrA, hfq, and smpB, in Salmonella is attenuated for mouse virulence and unable to survive in macrophages. CsrA has a clearly defined specificity based on binding to a specific mRNA sequence to inhibit translation. However, the proteins regulated by Hfq and SmpB are not as clearly defined. Previous work identified proteins regulated by hfq using purification of the RNA-protein complex with direct sequencing of the bound RNAs and found binding to a surprisingly large number of transcripts. In this report we have used global proteomics to directly identify proteins regulated by Hfq or SmpB by comparing protein abundance in the parent and isogenic hfq or smpB mutant. From these same samples we also prepared RNA for microarray analysis to determine if alteration of protein expression was mediated post-transcriptionally. Samples were analyzed from bacteria grown under four different conditions; two laboratory conditions and two that are thought to mimic the intracellular environment. We show that mutants of hfq and smpB directly or indirectly modulate at least 20% and 4% of all possible Salmonella proteins, respectively, with limited correlation between transcription and protein expression. These proteins represent a broad spectrum of Salmonella proteins required for many biological processes including host cell invasion, motility, central metabolism, LPS biosynthesis, two-component regulatory systems, and fatty acid metabolism. Our results represent one of the first global analyses of post-transcriptional regulons in any organism and suggest that regulation at the translational level is widespread and plays an important role in virulence regulation and environmental adaptation for Salmonella
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