Search results for: drug response
These transcriptomic signatures were made using data from the Cancer Therapeutics Response Portal (CTRP) project. The data includes 860 cancer cell lines and combines basal (untreated) gene expression with measurements of sensitivity to 481 anti-cancer compounds. Drug sensitivity was measured as cell viability (ATP levels measured by CellTiter-Glo®) over a sixteen-point concentration-response...
The iLINCS (Integrative LINCS) portal portal facilitates analysis of transcriptional drug signatures, and search for and analysis of groups of concordant transcriptional signatures of different drugs. The transcriptional signatures of chemical perturbagen activity in the iLINCS portal are constructed based on the Broad L1000 assay data. Each signature consists of the average z-scores and...
In the following work-flow example, we will start with a prototypical drug and will identify sets of drugs that have similar transcriptional signatures. Moreover, we will also pinpoint genes and pathways that are affected by the drug.
1. First, let's open Signatures Pipeline starting with the iLINCS homepage as shown below.
2. This will take you to a Signatures pipeline landing page that lists...
Signatures of perturbations assayed by P100 against 96 phosphopeptide probes and GCP assay against ~60 probes that monitor combinations of post-translational modifications on histones. The data is generated by using mass spectrometry techniques to characterize proteome level molecular signatures of responses to small molecule and genetic pertubations in a number of different cell lines.
Matching directly transcriptional signatures of a disease with negatively correlated transcriptional signatures of chemical perturbations (CP) underlies the Connectivity Map (CMap) approach to identifying potential drug candidates. Similarly, correlating signatures of chemical perturbagens with genetic perturbations of specific genes has been used to identify putative targets of drugs and other...
Reverse-phase protein array (RPPA) is a high-throughput technology that performs protein assays on thousands of samples simultaneously that measure the levels of protein expression, as well as protein modifications such as phosphorylation. Protein lysates are arrayed as microspots on nitrocellulized coated glass slides and probed with highly specific antibodies that have been validated for RPPA...
The perturbagen connectivity analysis compares the query signature to all signatures
for a given perturbagen as a group, thus extending the pair-wise connectivity analysis
to account for diversity of responses in different cellular contexts. This
is accomplished by performing the enrichment analysis of individual connectivity
scores between the query signature and set of all L1000 signatures of a...
Tutorial-1: iLINCS landing page Navigation.
Tutorial-2: Analyze my genes against LINCS datasets.
Tutorial-3: Analyze LINCS transcriptomic and proteomic datasets.
Tutorial-4: Analyze a drug signature and find other drugs with similar signatures.
Tutorial-5: Datasets workflow.
Tutorial-6: Signature workflow.
Tutorial-7: Genes workflow.
The P100 assay is a mass spectrometry-based targeted phosphoproteomic assay that detects and quantifies a representative set of 96 phosphopeptide probes. Phosphopeptides are enriched via an automated protocol and then mixed with a set of isotopically-labeled internal standards that correspond to the analytes in the P100 assay. This mixture is introduced into a mass spectrometer using ultra-high...
X2K is a tool for identifying drugs that induce or reverse the expression of lists of differentially expressed genes. (https://maayanlab.cloud/X2K/)
In the following example, we will try to identify a signature(s) that would reverse activated Estrogen receptor transcriptional signature profile. First, we will select Estradiol treatment perturbagen signature in MCF7 (ER+ breast cancer cell line) and then will identify highly disconnected (opposite) signature(s) to reverse its transcriptional signature profile via either gene loss-of-function...
L1000 fireworks display (L1000FWD) is a web application that provides interactive visualization of over 16000 drug and small-molecule induced gene expression signatures. (https://maayanlab.cloud/L1000FWD/)
iLINCS (Integrative LINCS) is an integrative web platform for analysis of LINCS data and signatures. The portal provides biologists-friendly user interfaces for analyzing transcriptomics and proteomics LINCS datasets. The portal integrates R analytical engine via several R tools for web-computing (rserve, opencpu, Shiny, rgl) and DCIC developed web tools and applications (FTreeView, Enrichr) into...
In the following example, we will start with a gene knockdown (loss-of-function) transcriptional signature and will try to identify a drug or sets of drugs that have opposite transcriptional signatures. For this example, we will look at MTOR gene knockdown in PC3, prostate cancer cells; will compare its transcriptional signature to the known MTOR inhibitor drug, Sirolimus (Rapamycin) signature and...
Use:
iLINCS's web-based tools and services are free for academic, non-profit and non-academic use.
Citation:
Within any publication that uses any methods or results inspired by iLINCS, please cite:
Connecting omics signatures of diseases, drugs, and mechanisms of actions with iLINCS
Marcin Pilarczyk, Mehdi Fazel-Najafabadi, Michal Kouril, Behrouz Shamsaei, Juozas Vasiliauskas, Wen Niu, Naim Mahi...
The iLINCS (Integrative LINCS) portal is an web platform for analysis of LINCS data and signatures. The portal provides biologists-friendly user interfaces for analyzing transcriptomics and proteomics LINCS datasets. iLINCS web tools facilitate statistical analysis to identify differentially expressed genes and proteins; bioinformatics analysis to identify affected networks, pathway and gene lists...
In the "Signatures" pipeline, you may explore, analyze and visualize over 200,000 pre-computed signatures (i.e. list of "scores" (activity levels) for a list of genes or for all genes in the genome "genome-wide signatures"). One would land on the Signatures landing page by clicking "Signatures" on the iLINCS portal header.
As shown in the figure above, there are 9 pre-computed signature libraries...
GR calculator
GREIN
Signeta