Search results for: iLINCS
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...
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...
There is an extensive workflow in iLINCS API repository (https://github.com/uc-bd2k/ilincsAPI) to show how to embed iLINCS functionalities in R. This repository consists of set of examples to showcase the ways of interacting with iLINCS APIs.
Depending on the exact type of the query signature, the connectivity analysis with libraries of
pre‐computed iLINCS signature are computed using different connectivity metric.
If the query signature is selected from iLINCS libraries of pre‐computed signatures, the
connectivity with all other iLINCS signatures is pre‐computed using the extreme Pearson’s
correlation signed significances of all...
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...
iLINCS pre-calculated signature connectivity is based on extreme correlation analysis, on the other hand, the uploaded signatures' similarity is based on weighted correlation calculation, please see the method section (https://www.nature.com/articles/s41467-022-32205-3).
The transcriptomics or proteomics signature is constructed by comparing expression levels of
two groups of samples (treatment group and baseline group) using Empirical Bayes linear model
implemented in the limma package. For the GREIN collection of GEO RNA‐seq datasets, the
signatures are constructed using the negative‐binomial generalized linear model as implemented
in the edgeR package.
1. Search is a very important part of this portal given that the number of LINCS datasets and precomputed signatures is constantly growing. One is able to search for a LINCS dataset and/or precomputed signature of interest on iLINCS portal in a couple of ways. In the example below, we will search for LINCS dataset for MCF7 cell line (the example of locating precomputed signature of interest is...
Please visit:
iLINCS Workshop at LINCS Symposium Nov, 2020 and
Adverse Outcome Pathways with iLINCS - DEPHS Seminar for general workflows.
Alternatively you can go to iLINCS Video Portal for a complete set of tutorial videos.
You may interrogate gene and protein expression patterns in datasets and signatures for a selected set of genes of interest. In the example below, we are going to query a chosen set of genes in one of the LINCS datasets; we will interrogate MEP_LINCS RNA-seq dataset EDS-1014 for user-submitted list of genes of interest.
1. First, let's open Genes pipeline starting with the iLINCS homepage as...
1. Search is a very important part of this portal given that the number of LINCS datasets and precomputed signatures is constantly growing. One is able to search for a LINCS dataset and/or precomputed signature of interest on iLINCS portal in a couple of ways. In the example below, we will search for a precomputed signatures for MCF7 cell line (the example of locating LINCS dataset of interest is...
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...
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...
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...
The iLINCS (Integrative LINCS) portal facilitates interrogation of LINCS transcriptomic and proteomic datasets with user-defined gene lists. The workflow is as follows:
Paste a list of gene IDs (Entrez Gene IDs or HGNC approved symbols) or create one from a library of gene lists.
Select a LINCS or non-LINCS dataset for analysis
Perform statistical analysis of differential gene or protein...
An experiment may have a number of samples which are organized in different groups (sample subgroupings). One may wish to restrict analysis to only a subset of all the available samples for an experiment. If you are interested in the analysis of differentially expressed genes between two groups of samples, you may create a two-group sample differential expression signature by clicking "Create...
1. One may also search for pre-computed signatures with pharmacological actions. To do this, let's click "Find Signatures with Pharmacological Actions" button on the bottom of Signatures pipeline landing page as shown below.
2. Clicking "Find Signatures with Pharmacological Actions" button will open a search field to input desired pharmacological actions as seen in the figure below. iLINCS will...
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...
One may wish to restrict analysis to only a subset of all the available samples for an experiment. We have described earlier how to generate a two-group sample differential expression signature by clicking "Create a Signature". The following section will explain how to find differentially expressed genes between multiple groups of samples.
1. To find differentially expressed genes between multiple...
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...
1. One may be interested to see all the metadata available for a particular precomputed signature. Let's say we would like to see more information for "LINCSCP_131839" signature. Let's click on the signature title as shown in the figure below.
2. As seen in the figure below, clicking on the signature title, opens up a new window containing a landing page for that particular signature. Similar...
"Genes" pipeline allows a query of genes of interest against LINCS data. One may start a query by inputing a list of genes via Entrez gene IDs or gene symbols separated by comma in the search field and clicking "Search for set of gene symbols or IDs". This section describes how to submit your own list of genes for analysis.
The figure above shows the screen to submit your own list of genes. You...
"Create a signature" function generates a two-group sample differential expression signature within a selected dataset using top 100 differentially expressed genes between the groups as seen in the figure below. You may adjust the number of included genes for the signature creation. You can select a different set of differentially expressed genes based on different cutoff (fold change and p-values...
Use case-1: Detecting and modulating mTOR pathway signaling.
Use case-2: Proteo-genomics analysis of cancer driver events in breast cancer.
Use case-3: Using iLINCS for analysis of transcriptional signature of COVID-19 infection.
TCGA datasets are mRNA-seq data generated by The Cancer Genome Atlas project.
The following cancers have been selected for study by TCGA because of their relatively poor prognosis and overall public health impact, as well as the availability of tumor and matched normal tissues that meet TCGA standards for patient consent, quality and quantity.
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.
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...
As seen in the figure below, clicking "Analyze" button next to any of the datasets, opens up a new window containing a landing page for that particular dataset.
The figure above shows the landing page for the dataset with LINCS ID # EDS-1014. The typical dataset landing page layout contains a short dataset description, reference, exploratory tools and dataset analysis tools. On the bottom of the...
Gene Expression Omnibus Datasets (GDS) is a public functional genomics data repository supporting MIAME-compliant data submissions. Array- and sequence-based data are accepted. Tools are provided to help users query and download experiments and curated gene expression profiles.
The GEO DataSets database stores original submitter-supplied records (Series, Samples and Platforms) as well as curated...
The Library of Integrated Network-Based Cellular Signatures (LINCS) Program aims to create a network-based understanding of biology by cataloging changes in gene expression and other cellular processes that occur when cells are exposed to a variety of perturbing agents.
The LINCS Data and Signature Generation Centers produce a variety of data for the library. For such data to be standardized...
An omics signature is a high‐dimensional readout of cellular state change that provides information about the biological processes affected by the perturbation which underlie the post‐perturbation phenotype of the cell. The signature in itself also provides information, although not always directly discernable, about the molecular mechanisms by which the perturbation causes observed changes. If we...
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