22,218 research outputs found
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
Sensitivity dependent model of protein-protein interaction networks
The scale free structure p(k)~k^{-gamma} of protein-protein interaction
networks can be reproduced by a static physical model in simulation. We inspect
the model theoretically, and find the key reason for the model to generate
apparent scale free degree distributions. This explanation provides a generic
mechanism of "scale free" networks. Moreover, we predict the dependence of
gamma on experimental protein concentrations or other sensitivity factors in
detecting interactions, and find experimental evidence to support the
prediction.Comment: organization improved, and experimental evidence of predicted
dependence on sensitivity is addresse
DART-ID increases single-cell proteome coverage.
Analysis by liquid chromatography and tandem mass spectrometry (LC-MS/MS) can identify and quantify thousands of proteins in microgram-level samples, such as those comprised of thousands of cells. This process, however, remains challenging for smaller samples, such as the proteomes of single mammalian cells, because reduced protein levels reduce the number of confidently sequenced peptides. To alleviate this reduction, we developed Data-driven Alignment of Retention Times for IDentification (DART-ID). DART-ID implements principled Bayesian frameworks for global retention time (RT) alignment and for incorporating RT estimates towards improved confidence estimates of peptide-spectrum-matches. When applied to bulk or to single-cell samples, DART-ID increased the number of data points by 30-50% at 1% FDR, and thus decreased missing data. Benchmarks indicate excellent quantification of peptides upgraded by DART-ID and support their utility for quantitative analysis, such as identifying cell types and cell-type specific proteins. The additional datapoints provided by DART-ID boost the statistical power and double the number of proteins identified as differentially abundant in monocytes and T-cells. DART-ID can be applied to diverse experimental designs and is freely available at http://dart-id.slavovlab.net
Deducing topology of protein-protein interaction networks from experimentally measured sub-networks.
BackgroundProtein-protein interaction networks are commonly sampled using yeast two hybrid approaches. However, whether topological information reaped from these experimentally-measured sub-networks can be extrapolated to complete protein-protein interaction networks is unclear.ResultsBy analyzing various experimental protein-protein interaction datasets, we found that they are not random samples of the parent networks. Based on the experimental bait-prey behaviors, our computer simulations show that these non-random sampling features may affect the topological information. We tested the hypothesis that a core sub-network exists within the experimentally sampled network that better maintains the topological characteristics of the parent protein-protein interaction network. We developed a method to filter the experimentally sampled network to result in a core sub-network that more accurately reflects the topology of the parent network. These findings have fundamental implications for large-scale protein interaction studies and for our understanding of the behavior of cellular networks.ConclusionThe topological information from experimental measured networks network as is may not be the correct source for topological information about the parent protein-protein interaction network. We define a core sub-network that more accurately reflects the topology of the parent network
Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry.
We used on-line electron capture dissociation (ECD) for the large scale identification and localization of sites of phosphorylation. Each FT-ICR ECD event was paired with a linear ion trap collision-induced dissociation (CID) event, allowing a direct comparison of the relative merits of ECD and CID for phosphopeptide identification and site localization. Linear ion trap CID was shown to be most efficient for phosphopeptide identification, whereas FT-ICR ECD was superior for localization of sites of phosphorylation. The combination of confident CID and ECD identification and confident CID and ECD localization is particularly valuable in cases where a phosphopeptide is identified just once within a phosphoproteomics experiment
Recommended from our members
A mass spectrometry-guided genome mining approach for natural product peptidogenomics.
Peptide natural products show broad biological properties and are commonly produced by orthogonal ribosomal and nonribosomal pathways in prokaryotes and eukaryotes. To harvest this large and diverse resource of bioactive molecules, we introduce here natural product peptidogenomics (NPP), a new MS-guided genome-mining method that connects the chemotypes of peptide natural products to their biosynthetic gene clusters by iteratively matching de novo tandem MS (MS(n)) structures to genomics-based structures following biosynthetic logic. In this study, we show that NPP enabled the rapid characterization of over ten chemically diverse ribosomal and nonribosomal peptide natural products of previously unidentified composition from Streptomycete bacteria as a proof of concept to begin automating the genome-mining process. We show the identification of lantipeptides, lasso peptides, linardins, formylated peptides and lipopeptides, many of which are from well-characterized model Streptomycetes, highlighting the power of NPP in the discovery of new peptide natural products from even intensely studied organisms
Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes
Complexes of physically interacting proteins constitute fundamental
functional units responsible for driving biological processes within cells. A
faithful reconstruction of the entire set of complexes is therefore essential
to understand the functional organization of cells. In this review, we discuss
the key contributions of computational methods developed till date
(approximately between 2003 and 2015) for identifying complexes from the
network of interacting proteins (PPI network). We evaluate in depth the
performance of these methods on PPI datasets from yeast, and highlight
challenges faced by these methods, in particular detection of sparse and small
or sub- complexes and discerning of overlapping complexes. We describe methods
for integrating diverse information including expression profiles and 3D
structures of proteins with PPI networks to understand the dynamics of complex
formation, for instance, of time-based assembly of complex subunits and
formation of fuzzy complexes from intrinsically disordered proteins. Finally,
we discuss methods for identifying dysfunctional complexes in human diseases,
an application that is proving invaluable to understand disease mechanisms and
to discover novel therapeutic targets. We hope this review aptly commemorates a
decade of research on computational prediction of complexes and constitutes a
valuable reference for further advancements in this exciting area.Comment: 1 Tabl
- …