Abstract:
BACKGROUND:Drug combinations have the potential to improve efficacy while limiting toxicity. To robustly identify synergistic combinations, high-throughput screens using full dose-response surface are desirable but require an impractical number of data points. Screening of a sparse number of doses per drug allows to screen large numbers of drug pairs, but complicates statistical assessment of synergy. Furthermore, since the number of pairwise combinations grows with the square of the number of drugs, exploration of large screens necessitates advanced visualization tools. RESULTS:We describe a statistical and visualization framework for the analysis of large-scale drug combination screens. We developed an approach suitable for datasets with large number of drugs pairs even if small number of data points are available per drug pair. We demonstrate our approach using a systematic screen of all possible pairs among 108 cancer drugs applied to melanoma cell lines. In this dataset only two dose-response data points per drug pair and two data points per single drug test were available. We used a Bliss-based linear model, effectively borrowing data from the drug pairs to obtain robust estimations of the singlet viabilities, consequently yielding better estimates of drug synergy. Our method improves data consistency across dosing thus likely reducing the number of false positives. The approach allows to compute p values accounting for standard errors of the modeled singlets and combination viabilities. We further develop a synergy specificity score that distinguishes specific synergies from those arising with promiscuous drugs. Finally, we developed a summarized interactive visualization in a web application, providing efficient access to any of the 439,000 data points in the combination matrix ( http://www.cmtlab.org:3000/combo_app.html ). The code of the analysis and the web application is available at https://github.com/arnaudmgh/synergy-screen . CONCLUSIONS:We show that statistical modeling of single drug response from drug combination data can help determine significance of synergy and antagonism in drug combination screens with few data point per drug pair. We provide a web application for the rapid exploration of large combinatorial drug screen. All codes are available to the community, as a resource for further analysis of published data and for analysis of other drug screens.
journal_name
BMC Bioinformaticsjournal_title
BMC bioinformaticsauthors
Amzallag A,Ramaswamy S,Benes CHdoi
10.1186/s12859-019-2642-7subject
Has Abstractpub_date
2019-02-18 00:00:00pages
83issue
1issn
1471-2105pii
10.1186/s12859-019-2642-7journal_volume
20pub_type
杂志文章abstract:BACKGROUND:Classification and naming is a key step in the analysis, understanding and adequate management of living organisms. However, where to set limits between groups can be puzzling especially in clonal organisms. Within the Mycobacterium tuberculosis complex (MTC), the etiological agent of tuberculosis (TB), expe...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-224
更新日期:2011-06-02 00:00:00
abstract:BACKGROUND:Direct in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To be...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-393
更新日期:2010-07-22 00:00:00
abstract:BACKGROUND:Phylogenies capture the evolutionary ancestry linking extant species. Correlations and similarities among a set of species are mediated by and need to be understood in terms of the phylogenic tree. In a similar way it has been argued that biological networks also induce correlations among sets of interacting...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-470
更新日期:2010-09-20 00:00:00
abstract:BACKGROUND:Microorganisms display vast diversity, and each one has its own set of genes, cell components and metabolic reactions. To assess their huge unexploited metabolic potential in different ecosystems, we need high throughput tools, such as functional microarrays, that allow the simultaneous analysis of thousands...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-478
更新日期:2010-09-23 00:00:00
abstract:BACKGROUND:Genetic variations predispose individuals to hereditary diseases, play important role in the development of complex diseases, and impact drug metabolism. The full information about the DNA variations in the genome of an individual is given by haplotypes, the ordered lists of single nucleotide polymorphisms (...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-015-0651-8
更新日期:2015-07-16 00:00:00
abstract:BACKGROUND:Phylogenetic profiles record the occurrence of homologs of genes across fully sequenced organisms. Proteins with similar profiles are typically components of protein complexes or metabolic pathways. Various existing methods measure similarity between two profiles and, hence, the likelihood that the two prote...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-8-S4-S7
更新日期:2007-05-22 00:00:00
abstract:BACKGROUND:Protein remote homology detection is one of the central problems in bioinformatics, which is important for both basic research and practical application. Currently, discriminative methods based on Support Vector Machines (SVMs) achieve the state-of-the-art performance. Exploring feature vectors incorporating...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-S2-S3
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Interest in de novo genome assembly has been renewed in the past decade due to rapid advances in high-throughput sequencing (HTS) technologies which generate relatively short reads resulting in highly fragmented assemblies consisting of contigs. Additional long-range linkage information is typically used to ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-S9-S9
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Drug resistance testing is mandatory in antiretroviral therapy in human immunodeficiency virus (HIV) infected patients for successful treatment. The emergence of resistances against antiretroviral agents remains the major obstacle in inhibition of viral replication and thus to control infection. Due to the h...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1179-2
更新日期:2016-08-22 00:00:00
abstract:BACKGROUND:PCR has the potential to detect and precisely quantify specific DNA sequences, but it is not yet often used as a fully quantitative method. A number of data collection and processing strategies have been described for the implementation of quantitative PCR. However, they can be experimentally cumbersome, the...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-8-131
更新日期:2007-04-20 00:00:00
abstract:BACKGROUND:Protein-coding gene detection in prokaryotic genomes is considered a much simpler problem than in intron-containing eukaryotic genomes. However there have been reports that prokaryotic gene finder programs have problems with small genes (either over-predicting or under-predicting). Therefore the question ari...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-131
更新日期:2010-03-15 00:00:00
abstract:BACKGROUND:Novel sequence motifs detection is becoming increasingly essential in computational biology. However, the high computational cost greatly constrains the efficiency of most motif discovery algorithms. RESULTS:In this paper, we accelerate MEME algorithm targeted on Intel Many Integrated Core (MIC) Architectur...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-018-2276-1
更新日期:2018-08-13 00:00:00
abstract:BACKGROUND:Profile Hidden Markov Models (pHMMs) are a widely used tool for protein family research. Up to now, however, there exists no method to visualize all of their central aspects graphically in an intuitively understandable way. RESULTS:We present a visualization method that incorporates both emission and transi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-5-7
更新日期:2004-01-21 00:00:00
abstract:BACKGROUND:Adapter trimming is a prerequisite step for analyzing next-generation sequencing (NGS) data when the reads are longer than the target DNA/RNA fragments. Although typically used in small RNA sequencing, adapter trimming is also used widely in other applications, such as genome DNA sequencing and transcriptome...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-182
更新日期:2014-06-12 00:00:00
abstract:BACKGROUND:The miRNAs, a class of short approximately 22-nucleotide non-coding RNAs, often act post-transcriptionally to inhibit mRNA expression. In effect, they control gene expression by targeting mRNA. They also help in carrying out normal functioning of a cell as they play an important role in various cellular proc...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-14-266
更新日期:2013-09-04 00:00:00
abstract:BACKGROUND:DNA methylation changes are associated with a wide array of biological processes. Bisulfite conversion of DNA followed by high-throughput sequencing is increasingly being used to assess genome-wide methylation at single-base resolution. The relative slowness of most commonly used aligners for processing such...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-337
更新日期:2014-10-18 00:00:00
abstract:BACKGROUND:Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods. RESULTS:On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-014-0383-1
更新日期:2014-12-10 00:00:00
abstract:BACKGROUND:Aptamers are nucleic acids selected for their ability to bind to molecules of interest and may provide the basis for a whole new class of medicines. If the aptamer is simply a dsDNA molecule with a ssDNA overhang (a "sticky" end) then the segment of ssDNA that complements that overhang provides a known bindi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-8-S7-S11
更新日期:2007-11-01 00:00:00
abstract::Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these ca...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-8-S6-S9
更新日期:2007-09-27 00:00:00
abstract:BACKGROUND:The adaptation of the CRISPR-Cas9 system to pooled library gene knockout screens in mammalian cells represents a major technological leap over RNA interference, the prior state of the art. New methods for analyzing the data and evaluating results are needed. RESULTS:We offer BAGEL (Bayesian Analysis of Gene...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1015-8
更新日期:2016-04-16 00:00:00
abstract:BACKGROUND:Melanoma results in the vast majority of skin cancer deaths during the last decades, even though this disease accounts for only one percent of all skin cancers' instances. The survival rates of melanoma from early to terminal stages is more than fifty percent. Therefore, having the right information at the r...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-020-3351-y
更新日期:2020-03-11 00:00:00
abstract:BACKGROUND:Emerging and re-emerging infectious diseases such as Zika, SARS, ncovid19 and Pertussis, pose a compelling challenge for epidemiologists due to their significant impact on global public health. In this context, computational models and computer simulations are one of the available research tools that epidemi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-020-03648-6
更新日期:2020-09-16 00:00:00
abstract:BACKGROUND:XHMM is a widely used tool for copy-number variant (CNV) discovery from whole exome sequencing data but can require hours to days to run for large cohorts. A more scalable implementation would reduce the need for specialized computational resources and enable increased exploration of the configuration parame...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-3108-7
更新日期:2019-10-11 00:00:00
abstract:BACKGROUND:Next Generation Sequencing techniques are producing enormous amounts of biological sequence data and analysis becomes a major computational problem. Currently, most analysis, especially the identification of conserved regions, relies heavily on Multiple Sequence Alignment and its various heuristics such as p...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-14-S11-S2
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Clustering techniques are routinely used in gene expression data analysis to organize the massive data. Clustering techniques arrange a large number of genes or assays into a few clusters while maximizing the intra-cluster similarity and inter-cluster separation. While clustering of genes facilitates learnin...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-40
更新日期:2009-01-30 00:00:00
abstract:BACKGROUND:Two of the main objectives of the genomic and post-genomic era are to structurally and functionally annotate genomes which consists of detecting genes' position and structure, and inferring their function (as well as of other features of genomes). Structural and functional annotation both require the complex...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-6-198
更新日期:2005-08-05 00:00:00
abstract:BACKGROUND:Introduction of spaced speeds opened a way of sensitivity improvement in homology search without loss of search speed. Since then, the efforts of finding optimal seed which maximizes the sensitivity have been continued today. The sensitivity of a seed is generally computed by its hit probability. However, th...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-S1-S37
更新日期:2010-01-18 00:00:00
abstract:BACKGROUND:Transposable elements (TE) are mobile genetic entities present in nearly all genomes. Previous work has shown that TEs tend to have a different nucleotide composition than the host genes, either considering codon usage bias or dinucleotide frequencies. We show here how these compositional differences can be ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-5-94
更新日期:2004-07-13 00:00:00
abstract:BACKGROUND:The immune system is multifaceted, structured by diverse components that interconnect using multilayered dynamic cellular processes. Genomic technologies provide a means for investigating, at the molecular level, the adaptations of the immune system in host defense and its dysregulation in pathological condi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1012-y
更新日期:2016-04-18 00:00:00
abstract:BACKGROUND:FREGENE simulates sequence-level data over large genomic regions in large populations. Because, unlike coalescent simulators, it works forwards through time, it allows complex scenarios of selection, demography, and recombination to be modelled simultaneously. Detailed tracking of sites under selection is im...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-9-364
更新日期:2008-09-08 00:00:00