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The LINCS L1000 is a high-throughput, reduced representation gene expression profiling assay developed as part of the NIH Library of Integrated Network-Based Cellular Signatures (LINCS) Program. L1000 directly measures 978 landmark genes and computationally infers the expression of 11,350 additional genes, enabling cost-effective large-scale transcriptional profiling at approximately $2 per sample. The technology was developed to create a Connectivity Map (CMap) that catalogs cellular responses to genetic and chemical perturbations, facilitating drug discovery, mechanism of action determination, and functional annotation of genetic variants. The LINCS L1000 dataset comprises over 1.3 million gene expression profiles representing responses to 19,811 chemical compounds, genetic perturbations targeting 5,075 genes (via shRNA knockdowns and cDNA overexpression), and 314 biologics across multiple cell lines and time points.
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| ID | Name | URL | Category | Format | Description |
|---|---|---|---|---|---|
| lincs-l1000.cmap | LINCS Connectivity Map (CMap) | clue.io | Graphical Interface | http | The Connectivity Map (CMap) database ... |
| lincs-l1000.clue | CLUE Platform | clue.io | Graphical Interface | http | The CLUE platform provides interactiv... |
| lincs-l1000.geo ⚠ | LINCS L1000 GEO Dataset | acc.cgi?acc=GSE92742 | Product | http | LINCS L1000 data deposited in the Gen... |
| ID | Name | URL | Category | Format | Relation | Description |
|---|---|---|---|---|---|---|
| spoke.graph | SPOKE Graph | data-tools | Graph | http | had primary source | The SPOKE knowledge graph containing ... |
| alzkb.browser | AlzKB Graph Database Browser | login | Graphical Interface | http | had primary source | A browser interface for a knowledge g... |
| alzkb.data | AlzKB Data Release (Version 2.0.0) | v2.0.0 | Graph | mixed | had primary source | Memgraph data release for AlzKB. |
| harmonizome.downloads | Harmonizome Downloads | download | Product | mixed | was derived from | Harmonizome 3.0 processed dataset dow... |
| harmonizome.kg-neo4j | Harmonizome Knowledge Graph Neo4j Database | harmonizome-kg.maayanlab.cloud | Graph | neo4j | was derived from | Neo4j knowledge graph serialization o... |
| spoke-okn.graph | SPOKE-OKN Graph | spoke.ucsf.edu | Graph | ttl | was influenced by | The SPOKE-OKN knowledge graph, an OKN... |
| reprotox-kg.graph.sigcom-lincs | ReproTox-KG SigCom LINCS Drug-Gene Graph | sigcom_lincs_serialization.valid.json (109.3 MB) | Graph | json | had primary source | Drug-to-gene up- and down-regulation ... |
| reprotox-kg.graph.drug-similarity | ReproTox-KG LINCS Drug Similarity Graph | sigcom_lincs_drug_similarity.valid.json (14.3 MB) | Graph | json | had primary source | Drug-drug cosine similarity edges com... |
| drugenrichr.libraries | DrugEnrichr Drug Set Libraries | datasetStatistics (4.2 KB) | Product | json | had primary source | Statistics for the 29 drug set librar... |
| drugshot.l1000-similarity | L1000 Drug-Drug Similarity Matrix | L1000_coexpression.h5 (1.4 GB) | Product | hdf5 | had primary source | Drug-drug similarity matrix from cosi... |
| sigcom-lincs.cp-consensus | L1000 Chemical Perturbation Consensus Signatures | cp_mean_coeff_mat.tsv.gz (1.8 GB) | Product | tsv | had primary source | Consensus (mean) characteristic-direc... |
| sigcom-lincs.xpr-consensus | L1000 CRISPR Knockout Consensus Signatures | xpr_mean_coeff_mat.tsv.gz (412.5 MB) | Product | tsv | had primary source | Consensus (mean) characteristic-direc... |
| sigcom-lincs.cp-gmt | L1000 Chemical Perturbation Gene Sets | l1000_cp.gmt (2.1 GB) | Product | tsv | had primary source | Up and down gene sets for each L1000 ... |
| sigcom-lincs.xpr-gmt | L1000 CRISPR Knockout Gene Sets | l1000_xpr.gmt (418.1 MB) | Product | tsv | had primary source | Up and down gene sets for each L1000 ... |
| sigcom-lincs.shrna-gmt | L1000 shRNA Gene Sets | l1000_shRNA.gmt (478.4 MB) | Product | tsv | had primary source | Up and down gene sets for each L1000 ... |
| sigcom-lincs.oe-gmt | L1000 Overexpression Gene Sets | l1000_oe.gmt (101.1 MB) | Product | tsv | had primary source | Up and down gene sets for each L1000 ... |
| sigcom-lincs.cp-coefficients | L1000 Chemical Perturbation Signature Matrix | cp_coeff_mat.gctx (33.6 GB) | Product | hdf5 | had primary source | Characteristic-direction coefficient ... |
| sigcom-lincs.drug-similarity | L1000 Drug-Drug Similarity Matrix | L1000_2021_cosine_drug_similarity_lm.h5 (4.2 GB) | Product | hdf5 | had primary source | Drug-drug cosine similarity matrix co... |
| sigcom-lincs.gene-similarity | L1000 Gene-Gene Similarity Matrix | L1000_2021_cosine_gene_similarity_lm.h5 (215.3 MB) | Product | hdf5 | had primary source | Gene-gene cosine similarity matrix co... |
| drugmonizome.libraries ⚠ | Drugmonizome Drug Set Libraries | libraries | Product | json | was derived from | The 35 Drugmonizome drug set librarie... |
| l1000fwd.portal ⚠ | L1000FWD Web Application | l1000fwd | Graphical Interface | http | was derived from | Interactive fireworks and t-SNE maps ... |
| l1000fwd.api ⚠ | L1000FWD API | api_page | Programming Interface | json | was derived from | REST API for searching drugs by name ... |
| l1000fwd.cd-signatures-landmark | L1000FWD CD Signatures (Landmark Genes) | CD_signatures_LM_42809x978.gctx (330.6 MB) | Product | hdf5 | was derived from | Characteristic direction (CD) signatu... |
| l1000fwd.cd-signatures-full | L1000FWD CD Signatures (Full Space) | CD_signatures_full_42809x22268.gctx (7.1 GB) | Product | hdf5 | was derived from | Characteristic direction (CD) signatu... |
| l1000fwd.adjacency-matrix | L1000FWD Signature Adjacency Matrix | Adjacency_matrix_LM_space_42809x42809.gctx (13.7 GB) | Product | hdf5 | was derived from | Cosine similarity adjacency matrix am... |
| l1000fwd.gene-sets-gmt | L1000FWD Signature Gene Sets (GMT) | CD_signatures_binary_42809.gmt (115.0 MB) | Product | tsv | was derived from | Up and down gene sets for the 42,809 ... |
| l1000fwd.gene-sets-json | L1000FWD Signature Gene Sets (JSON) | CD_signatures_binary_42809.json (169.5 MB) | Product | json | was derived from | Up and down gene sets for the 42,809 ... |
| l1000fwd.signature-metadata | L1000FWD Signature Metadata | CD_signature_metadata.csv (4.8 MB) | Product | csv | was derived from | Metadata for the L1000FWD signatures ... |
| l1000fwd.drug-metadata | L1000FWD Drug Metadata | Drugs_metadata.csv (7.4 MB) | Product | csv | was derived from | Metadata for the profiled drugs and s... |
| l1000fwd.probes-landmark-metadata | L1000FWD Landmark Probe Metadata | Probes_L1000_metadata.csv (16.3 KB) | Product | csv | was derived from | Metadata for the L1000 probes of the ... |
| l1000fwd.probes-full-metadata | L1000FWD Full Probe Metadata | Probes_full_metadata.csv (364.2 KB) | Product | csv | was derived from | Metadata for the 22,268 probes used i... |
| sep-l1000.portal | SEP-L1000 Web Portal | SEP-L1000 | Graphical Interface | http | was derived from | Web portal for browsing and searching... |
| sep-l1000.lincs-signatures | SEP-L1000 LINCS L1000 CD Signatures | LINCS_Gene_Experssion_signatures_CD.csv.gz (38.6 MB) | Product | csv | was derived from | Characteristic direction gene express... |
| sep-l1000.go-signatures | SEP-L1000 GO-Transformed Signatures | GO_transformed_signatures_PAEA.csv.gz (219.9 MB) | Product | csv | was derived from | Gene Ontology transformed L1000 signa... |
| sep-l1000.maccs-fingerprints | SEP-L1000 MACCS Fingerprints | MACCS_bitmatrix.csv.gz (1.2 MB) | Product | csv | was derived from | 166-bit MACCS chemical fingerprint ma... |
| sep-l1000.strongest-signatures-metadata | SEP-L1000 Strongest Signature Metadata | meta_LINCS_strongest_signatures.csv (31.8 MB) | Product | csv | was derived from | Metadata mapping each LINCS L1000 com... |
| sep-l1000.probes-metadata | SEP-L1000 Probe Metadata | meta_Probes_info.csv (361.7 KB) | Product | csv | was derived from | Mapping of L1000 probes to gene symbols. |
| sep-l1000.smiles-metadata | SEP-L1000 Compound SMILES Metadata | meta_SMILES.csv (3.8 MB) | Product | csv | was derived from | Compound metadata for 41,774 LINCS L1... |
The LINCS L1000 platform represents a major advance in high-throughput transcriptional profiling technology. By measuring only 978 carefully selected “landmark” genes and using computational inference for the remaining transcriptome, L1000 achieves dramatic cost reduction (approximately $2 per sample) while maintaining high reproducibility and comparability to RNA-seq. This breakthrough enabled the generation of over 1.3 million gene expression profiles as part of the NIH LINCS Program, creating one of the largest publicly available transcriptional profiling resources.
171 high-confidence Perturbagen Classes have been defined, representing groups of perturbagens with shared mechanisms. These include:
PCLs enhance interpretability by aggregating similar perturbagens to strengthen on-target signals while diminishing off-target effects.
To mitigate strong off-target effects of shRNAs (where seed sequence effects often exceed on-target effects), a Consensus Gene Signature algorithm was developed that identifies consistent gene expression changes across multiple shRNAs targeting the same gene.
The Connectivity Map uses a weighted connectivity score (WTCS) approach similar to Gene Set Enrichment Analysis, computing similarity between query gene signatures and database signatures. Results are normalized and summarized across cell lines using quantile-based metrics (τ scores) to identify robust connections.
Primary Reference:
Additional Resources:
Supported by NIH grants including 5U54HG006093, U54HG008699, and 5U01HG008699 as part of the NIH Common Fund LINCS Program.
Created: January 08, 2025 | Last modified: September 23, 2026