AIG All Inferred Genes; includes the 978 landmark genes, plus the entire set of genes for which we infer expression in any given experiment, including the best inferred 9196 genes (BING) and 2154 additional genes whose expression is less well inferred by our algorithm.
BING Best Inferred Genes; includes the 978 landmark genes as well as 9196 non-landmark genes for which we reliably infer gene expression using a computational approach. The L1000 assay directly measures or infers the expression levels of 12,328 genes. By evaluating the current statistical model against a large compendium of RNA-Seq profiles from over 100 tissues from the GTEx consortium, we have identified a subset of 10,174 genes that are either measured or well inferred. This subset is known as the Best INferred Gene (BING) space.
BRD First 3 letters of each identifier for each perturbagen. Identifiers with a “K” following BRD have an unambiguous structure. Identifiers with an “A” following BRD are ambiguous in structure.
Brew CMap-specific name assigned to the last step of the espresso computational pipeline, in which biological replicate signatures (typically three) from each experiment are collapsed into a single signature using a moderated z-score (MODZ) procedure. This procedure mitigates the effects of uncorrelated or outlier data in replicates and thus generates a signature that more accurately reflects the transcriptional effects of a given perturbagen.
bead_batch One instantiation of a complete set of beads which have been coupled to probes at one time under the same conditions.
bead_revision The set of beads that applies to a particular collection of gene pairs for each bead color.
bead_set A pair of barcodes for each gene pair used for a bead color; gene pairs are used for the tag duo procedure, where a bead color is coupled to two different genes.
brew_prefix aka replicate set - the part of plate name (det_plate or rna_plate) that is independent of replicate, bead_batch and other. E.g. LJP005_A375_24H is the brew_prefix for the plates.LJP005_A375_24H_X1_B19, LJP005_A375_24H_X2_B19, LJP005_A375_24H_X3_B19
build A version of the cmap dataset and webtools. Each build is uniquely identified by the build number. New builds are released intermittently as new data and tools become available. Data and tools may also be retired between builds.
CGS Consensus Gene Signature; a signature, generated by an algorithm, that reflects the consistent gene expression effects of shRNAs that target the same gene. CGS was developed to distinguish the strong off-target effects of shRNAs, which are not shared, from on-target effects.
CSS Consensus seed signature; a signature, generated by an algorithm, that reflects the consistent gene expression effects of multiple shRNAs that target the same seed sequence but target different gene targets.
Cancer Cell Line Encyclopedia (CCLE) The Cancer Cell Line Encyclopedia (CCLE) project is a collaboration between the Broad Institute, the Novartis Institutes for Biomedical Research, and the Genomics Institute of the Novartis Research Foundation to conduct genetic and pharmacologic characterization of a large number of human cancer cell lines. The CCLE contains public access sequencing data and visualization of DNA copy number, mRNA expression, mutation data, and more for 1000 cell lines.
Cell Painting An imaged-based assay that uses fluorescent dyes to to detect morphological changes in a variety of cell features in response to perturbagen treatment.
Cell line / Cell type / Cellular model The in vitro model in which an L1000 experiment is performed. Typically, these cell lines model a certain disease and may harbor mutations or other genetic alterations of interest. A cancer cell line is a cell line derived from a cancerous tissue and established for continuous growth in vitro; these cells are used to study the biology of cancer and cancer treatment. An immortalized Cell Type refers to cells that originate from a particular tissue type and have acquired the ability to divide indefinitely and evade normal cellular senescence mechanisms. Cells may be immortal because they derive from a naturally occurring cancer; alternatively they may have been induced to become immortal through in vitro genetic manipulation.
Connectivity A measure of similarity between two signatures. Two signatures that have a very high positive connectivity score are said to be positively connected; two with a very high negative score are said to be negatively connected.
Connectivity Map Connectivity Map, or CMap, is a resource of over one million gene expression profiles from many cell types treated with chemical or genetic perturbagens, designed to probe relationships between diseases, cell physiology, and therapeutics.
Connectivity score A connectivity score is a value, between +100 and -100, that quantifies the relationship between a query signature (set of differentially expressed genes representing a biological state of interest) and a perturbagen. The connectivity score incorporates three components: 1) a nominal p-value (NP) that indicates the significance of the similarity (enrichment based on the Kolmogorov-Smirnov statistic) between query and reference signature compared to a null distribution of random queries, 2) a false discovery rate (FDR) value that adjusts the p-value to account for multiple hypothesis testing given the large numbers of comparisons in the dataset, and 3) 𝛕, which represents the effect size of a given enrichment score on a standardized scale. 𝛕 is a scale-free measure ranging from -100 to 100 and is the score that we report in query results; a 𝛕 of 90 indicates that only 10% of perturbations showed stronger connectivity to the query. Note that we don’t routinely calculate NP and FDR because empirically tau of >90 passes those tests.
Controls; Types of Controls are used to differentiate authentic perturbagen-induced changes in gene expression from artifacts and technical errors. PosCons refer to positive controls, which are perturbagen treatments known to induce strong changes in expression. Vehicle controls refer to negative controls that should not cause significant changes in expression.
Controls—PosCons perturbagens that generate well-understood gene expression signatures and thus serve as positive controls for each experimental plate. The following table lists compounds that can serve as poscons in L1000; the most frequently used compounds are highlighted with an asterisk.
Controls—Vehicles (VC) Various forms of “inert” experiments performed to determine, by contrast, effects that are specifically due to a perturbation as opposed to responses associated with handling cells or delivering a perturbagen; a type of negative control.
Core Cell Line Panel A set of nine cell lines that are typically used in L1000 assays to test the transcriptional effects of perturbagens. The core cell lines are: A375, A549, HA1E, HCC515, HT29, HEPG2, MCF7, PC3, VCAP. These lines were used to generate all the data in the Touchstone (TS) dataset. Cells that have been transfected by a particular Cas9-containing vector, such as 311 or 101, are named with the vector name appended to their cell line name. For example, HA1E cells that are transfected with 311 vector are named HA1E.311.
cell_id A shorthand CMap identifier number assigned to each cell line used in the L1000 assay.
cl_center_specific_id synonym for cell_id.
clue.io A secure, cloud-based computing environment, that allows both experienced and novice CMap users to interact with and analyze Connectivity Map data via a collection of robust and easy to use web-based applications.
count_cv The coefficient of variation of bead counts.
count_mean The mean of per well-analyte bead counts.
DEx database A database of differential expression signatures derived from comparisons using diseased tissue; for example, comparison of diseased to healthy tissue, or diseased tissue subject to pharmacological or other type of treatment over a time period. In general, DEx signatures have not been made by the CMap team using L1000; rather, they've been submitted by other labs to public data repositories such as GEO or MSigDB.
Dactyloscopy Dactyloscopy is an algorithm that is used to verify the identity of cell lines and confirm metadata in the descriptions of L1000 experiments. The algorithm is based on comparison of gene expression profiles measured in L1000 to baseline expression profiles, generated from RNAseq data, from the library of ~1000 cancer cell lines (Cancer Cell Line Encyclopedia). The Spearman correlation coefficient of an experimental expression profile should be highest against the reference profile of the actual cell line used in the L1000 experiment, when compared to the correlation coefficients against reference profiles of other cell lines in the library. The algorithm relies on the fact that baseline gene expression is cell line-specific, which together with the fact that most perturbagens significantly modulate expression of only a few genes, allows for unambiguous distinguishing of cell lines used in L1000.
Data Level Data level refers to the degree of mathematical processing that has been performed on L1000 data as it goes through the signature generation pipeline, which consists of five levels.
Deconvolution (d-peak) The computational method that assigns a data peak (from Level 1 data) to a specific gene is referred to as deconvolution, or d-peak.
Differential expression The degree to which a gene’s expression is increased or decreased in response to a perturbagen, relative to the absence of perturbagen treatment. In the L1000 pipeline, differential expression is computed using a robust z-score.
Discover dataset Data produced for discovery purposes; the assay conditions do not necessarily involve a majority of the CMap core cell lines and are not necessarily the standard experimental conditions used for the Touchstone dataset; moreover, discovery perturbagens may have tentative or no annotations.
Diversity score A metric that describes the diversity of the gene expression consequence of perturbagen treatment across different cell lines. This is also sometimes called inter-cell connectivity (ICC).
det_mode The detection mode used for acquiring L1000 data. Can be either DUO (two genes per analyte color) or UNI (one gene per analyte color).
det_plate Detection plate, the plate of L1000 experiments that, at the end of the assay pipeline, is put through the Luminex scanners to detect the levels of landmark gene amplicons.
det_well Detection well, which refers to each well of the detection plate in which an L1000 experiment is conducted.
distil_cc_q75 75th quantile of pairwise spearman correlations in landmark space of replicate level 4 profiles.
distil_id ID of an individual replicate profile, referred to as level 4 / z-score data, that is used in creating the signature from replicates assayed together on an L1000 plate. The signature is referred to as level 5 / aggregated z-score data.
distil_nsample Number of individual replicate profiles (level 4 / z-score) that were used to create the signature (level 5 / aggregate z-score).
distil_ss The number of significantly differentially expressed transcripts that arise from a particular perturbagen treatment.
down score A value between +1 and -1 representing the absolute enrichment of a down tag list in a given instance. The down score is the "down" value reported on the detailed result page and the result detail window. A high positive down score indicates that the corresponding perturbagen induced the expression of the probe sets in the down tag list. A high negative down score indicates that the corresponding perturbagen repressed the expression of the probe sets in the down tag list. The connectivity score is a combination of the up score and down score.
Espresso CMap-specific name assigned to the computational pipeline that processes raw L1000 data (LXB files of scan data for each experiment) through several steps to generate differential gene expression signatures.
Experiment (aka treatment, aka profile) Perturbagen treatment of cells at one experimental condition of cells, dose, and time-point
GCP GCP (global chromatin profiling) uses targeted mass-spectrometry technology to measure ~60 combinations of post-translational modifications on histones. GCP measures global histone modifications (e.g. di-methylation of lysine 27 on histone 3), rather than modifications at specific sites along the genome.
GCT Gene Cluster Text; a matrix-based file format containing numerical data as well as row and column annotations. For L1000 data, the columns of the matrix correspond to perturbagen-specific profiles, and the rows correspond to genes.
GCTx Gene Cluster Text x, a file format that enables structuring of content in an HDF5 file that is compatible with L1000 data. GCTx format allows for storage of every profile we generate in a single unified file to which new signatures can be appended as they are generated. Each column in the GCTX matrix is a signature and each row is a gene in that signature.
GRP file Gene set format file; contains a list of elements (typically gene symbols or feature identifiers) in a simple newline-delimited text format with one entry per line.
GTEx A database that catalogs gene expression profiles from many tissue types, to further our understanding of how changes in our genes and gene expression contribute to human diseases.
GUTC The Grand Unified Theory of Connectivity (GUTC) is a computational method that reduces the large, complex dataset of signatures arising from a query to a smaller, focused set of relevant connectivity results. Signature data is stored as a matrix, where each row is a landmark gene (~1000 total) and each column is a treatment. Currently there are at least 400,000 signatures in this matrix, and this number is growing. Thus, a user querying the database with an expression signature faces the prospect of sorting through at least 400,000 similarity scores. gutC is a computational method that reduces the amount of output data to a more manageable and meaningful set of scores.
Gene Set The pair of lists of up- and down- regulated genes in a biological condition of interest. For example, one could make a gene set of the genes induced and repressed following the exposure of a cell line to a small molecule relative to a vehicle control treatment. Any marker-selection algorithm or heuristic can be used to produce a gene set. It is possible to define a gene set from a signature by simply selecting the N most up- and/or down-regulated genes, or by selecting all genes with differential expression greater than some threshold value.
Genetic gain of function (GoF) A mutation in a gene that causes the gene product to acquire a new molecular function or a new pattern of gene expression. In the L1000 context, we often refer to genetic over-expression constructs as gain of function experiments, because they may result in aberrantly high expression of a particular gene of interest.
Genetic loss of function LoF A mutation in a gene that either prevents synthesis of the protein product or results in synthesis of a nonfunctional protein. In the L1000 context, we often refer to genetic knock down or knock out, via RNAi or CRISPR, as loss of function experiments, because they result in aberrantly low, or no, expression of a particular gene of interest.
gtex_id identifier for the sample as used within the GTEx project.
HG-U133A Affymetrix GeneChip Human Genome U133A Array (part number 510681). The probe sets on this array define the feature set.
Inference An algorithm that uses expression of the 978 Landmark genes in a given experiment to estimate expression of 11,350 additional genes.
Inferred gene A non-landmark gene whose expression in response to perturbagen treatment is estimated using an inference algorithm, rather than measured directly by L1000.
Instance A treatment and control pair and the list of probe sets ordered by their extent of differential expression between this treatment and control pair. The instance is the basic unit of data and metadata in cmap. Every instance has a number of attributes including a unique identifier (instance_id), the batch in which it was produced, the cmap name of the perturbagen, the source of that perturbagen, the concentration of that perturbagen, the cmap cell line used, and the scan numbers for the treatment and its control(s). All instances in the current build and their attributes are accessible from the instance page.
Introspect The act of querying the signatures within a dataset against each other to determine connectivities among them, as opposed to determining connectivities between each signature of the set and the Touchstone reference dataset.
Invariant gene A gene whose expression has been determined to be consistent across a wide variety of Affymetrix samples extracted from Gene Expression Omnibus (GEO)
iPSC Cells Induced pluripotent stem cells are cells, derived from skin or blood, that have been genetically altered to an embryonic stem cell state; these cells can then be induced to develop into any cell type.
icc Inter-cell connectivity (ICC). The similarity (aggregated WTCS) between signatures of a given perturbagen across cell lines. This number ranges between -1 and 1, and the higher the number, the more similar the signatures across cell lines. Only exemplar signatures are used in computing ICC. See is_exemplar for more details.
inf_model Inference model designation.
inst_id the identifier for the sample exactly as it appears in the matrix files attached to the series.
is_exemplar A boolean indicating whether the given signature is an exemplar. Due to the redundancy of the CMap database, meaning that some perturbagens have many signatures even within the same cell line, it is convenient to identify a single ‘exemplar’ signature for each perturbagen in each cell line. These signatures are specifically designated for further analysis, such as ICC and aggregate TAS. Exemplar signatures are generally picked based on TAS, such that the signature with the highest TAS is chosen as exemplar.
is_gold A heuristic for assessing whether a signature is reproducible and distinct. Requirements include: distil_cc_q75 >= 0.2 and pct_self_rank_q25 <= 0.05.
Kolmogorov-Smirnov statistic The non-parametric rank statistic upon which the cmap analytic is based. A detailed description of the Kolmogorov-Smirnov statistic can be found in Nonparametric Statistical Methods (second edition) by Myles Hollander and Douglas Wolfe (1999).
L1000 A high-throughput gene expression assay that measures the expression of approximately 1000 landmark genes in cells treated with perturbagens; this data is then used to infer expression of 11,350 additional genes. The L1000 assay contains 1058 probes for 978 landmark transcripts and 80 control transcripts chosen for their invariant expression. Briefly, the assay is performed as follows: Cells growing in 384-well plates are lysed and the mRNA transcripts captured on oligo-dT-coated plates. cDNAs are synthesized from the captured transcripts and subjected to LMA (ligation-mediated amplification) using locus-specific oligonucleotides harboring a unique 24-mer barcode sequence and a 5’biotin label. The biotinylated LMA products are detected by hybridization to polystyrene beads of distinct fluorescent color, each coupled to an oligonucleotide complementary to a barcode, and staining with streptavidin-phycoerythrin. Thus each bead is analyzed for its bead color (denoting the landmark identity) and the fluorescence intensity of the phycoerythrin signal (denoting the landmark transcript abundance). Because only 500 bead colors are commercially available, we devised a strategy that allows two transcripts to be identified by a single bead color.
LINCS DCIC Library of Network-Based Cellular Signatures Data Coordination and Integration Center, which is working to develop methods and tools to integrate and interact with the large genomics and proteomics datasets generated by the members of the LINCS consortium.
LISS Normalization The first of two normalization steps by which Level 2 data is converted to Level 3 data. The LISS (Luminex Invariant Set Normalization) step fits a power law curve to the median log2-intensities for the 10 invariant gene sets. This curve serves as a reference against which the experimental data are re-scaled, ultimately enabling conversion between measured Luminex intensity and Affymetrix log2-expression values.
Landmark gene One of the 978 genes that are measured directly using the L1000 assay. Each landmark represents a tight cluster of co-regulated genes, as determined from analysis of a large collection of publically available gene expression profiles.
Library of Network-based Cellular Signatures (LINCS) AN NIH program working to catalogue perturbagen-induced changes in gene expression and other cellular processes, in order to expand understanding of networks and pathways in biology.
Marker Selection Marker selection refers to the identification of genes that are differentially expressed under a defined condition (eg: perturbation). The Morpheus app contains a Marker Selection tool that generates from input data lists of the up- and down-regulated genes.
Molecular Signature Database (MSigDB) MSigDB is a database of annotated gene sets pertaining to biological pathways and processes in mammalian, primarily human, cells.
mfc_plate_dim Manufacturer’s stated dimensions of the pert plate.
mfc_plate_id Manufacturer’s designated plate id.
mfc_plate_name Name of the plate as designated by the manufacturer.
mfc_plate_quad Quadrant of the plate as designated by the manufacturer.
mfc_plate_well Well of the pert plate as designated by the manufacturer.
modZ Moderated Z score; produced by the weighted average of replicates, where weighting is proportional to the Spearman correlation between replicates.
Normalized enrichment score (NES) Enrichment score that has been rescaled to account for different query sizes, cell lines, and perturbagen types.
ngenes_modulated_dn_lm The number of landmark genes that show decreased expression in cells treated with perturbagen.
P-value An estimate of the likelihood that the enrichment of a set of instances in the list of all instances in a given result would be observed by chance. This value is determined empirically by computing the enrichment of one hundred thousand sets of instances selected at random from the set of all instances in the result.
P100 P100 uses targeted mass-spectrometry technology to measure 96 phosphopeptides that are commonly observed and modulated in diverse cell types. These phosphopeptides were chosen similarly to the way the 978 landmarks were chosen for L1000, as a way of representing the cellular state with incomplete information.
PBIOA Pooled L1000 bioactivity assay, where L1000 serves as a bioactivity sensor using pooled cell lines
PCL Perturbagen CLass, referring to CMap-designated groupings of compound and genetic perturbagens based on their strong connectivities to each other and their shared mechanisms of action or biological functions. Each PCL generally has 3 or more members.
PRISM A high-throughput screen for assessing cell viability in which cell lines that have each been labelled with a unique 24-nucleotide barcode are pooled and treated with the experimental condition, and surviving cells are “counted” through identification of the cognate barcode. PRISM is an acronym for Profiling Relative Inhibition Simultaneously in Mixture.
Peak deconvolution Also referred to as "dpeak", the computational method for assigning the correct expression level to each of the two genes whose transcripts bind to beads of the same analyte color.
Permuted signature A signature generated from the computation, done during the brew process, of collapsing random replicates into signatures to generate a null for comparison to actual signatures, to be used for replicate correlation and signature strength determinations.
Perturbagen Reagent used in the laboratory for cell treatment and determination of the resulting transcriptional response. Perturbagen types used primarily include small-molecule compounds (trt_cp), gene knockdowns using shRNAs (trt_shrna) and/or CRISPR (trt_xpr), and reagents that cause increased amounts of a target protein using cDNAs delivered with a vector (trt_oe). Perturbagens (or groups of closely related perturbagens) are identified by their cmap name. A single perturbagen may be represented by multiple instances.
Plate Map A plate map is the collection of metadata describing the perturbagen treatments and experimental conditions for each well in an L1000 assay plate.
Plate types Usually L1000 assays are carried out in 384 well plates. There are several types of plates used for the different parts of the assay. See Connectopedia for a list defining these plates, including the common term as well as the term that appears in data files.
Population Control (PC) A control against which gene expression changes are measured; the population control consists of the expression of each landmark gene in every well of the plate except the well(s) for the treatment of interest. In other words, a test with a given perturbagen will involve only one or a few wells in a 384-well plate; the other wells will serve as a population control for each landmark gene.
Primary Cells Cells that are taken from living tissue and established in vitro for study; because they go through very few doublings in vitro prior to experimental use, they closely mimic the tissue from which they originated.
Probe set The collection of match and mismatch oligonucleotides on an Affymetrix GeneChip microarray designed against a given transcript which together allow the relative level of that transcript to be estimated. Probe sets are uniquely identified with a code number that, by convention, ends with "_at" ( eg 200800_s_at). Tag lists and instances are populated with probe sets from the feature set. Detailed descriptions of individual probe sets can be found at the AffyMetrix NetAffx Analysis Center.
Profile A profile (also termed an experiment or an instance) corresponds to data generated from a single perturbagen, cell type, dose, and time point. The numbers in a profile represent either the raw fluorescent intensity values (level 1 or raw data) or these numbers post deconvolution (level 2) or post normalization (level 3). Profiles are compared to appropriate controls to generate a list of differentially expressed genes (level 4). Replicate level 4 profiles (typically 3) are collapsed via weighted averaging into one differentially expressed vector, which we term a signature (level 5).
pc The percent of total perturbagens, querying the column sample against the Touchstone dataset, that exceed the given thresholds
pc_selection The percent of total perturbagens, querying the column sample against selected rows, that exceed the given thresholds
pct_self_rank_q25 Self connectivity of replicates expressed as a percentage of total instances in a replicate set.
pert_desc A brief summary of the biological function (for genetic perturbagens) or mechanism of action (for compound perturbagens).
pert_dose Precise amount of compound used to treat cells.
pert_dose_unit Unit (generally micromolar) applied to the dose of compound used to treat cells.
pert_id A unique identifier for a perturbagen that refers to the perturbagen in general, not to any particular batch or sample.
pert_idose The concatenation of pert_dose and pert_dose_unit to create a string containing the dose information. We use a standardized dose for a perturbagen treatment. For example, the less common dose of 10.04 is rounded to 10. This enables grouping of signatures by a common dose.
pert_iname The internal (CMap-designated) name of a perturbagen. By convention, for genetic perturbations CMap uses the HUGO gene symbol.
pert_itime The concatenation of pert_time and pert_time_unit to create a string containing the length of time that a perturbagen was applied to the cells. We use a standardized time for a perturbagen treatment. For example, if data is made by treating cells with a perturbagen for 5.5 hours, we round that time to the more common treatment time of 6 hours.
pert_mfc_id A manufacturer's id for the perturbagen; by convention, for compounds registered with Broad Compound Management this is the full BRD containing both the compound ID and the batch ID.
pert_time The length of time, expressed as a number, that a perturbagen was applied to the cells; does not include the unit.
pert_time_unit The unit that applies to the pert_time numerical value.
pert_type Abbreviated designation for perturbagen type, referring to compound or genetic perturbagens that are used in cell treatments to assess gene expression effects. The various pert_types used by CMap are listed in the table below.
pert_vehicle The solvent or other vehicle used to deliver the perturbagen.
pool_id Landmark probe pool used; generally the pool is epison, and older pools such as delta and deltaprime are not relevant for most users.
provenance_code A shorthand code that tracks the different steps in data processing.
Quantile Normalization (QNORM) The second of two normalization steps by which Level 2 data is converted to Level 3 data. The QNORM step standardizes the shape of the expression profile distributions on each plate such that all of the data for a plate is on the same scale. Quantile normalization is then performed on all plates within a cohort to standardize the data across plates (Q2NORM).
Query Strictly speaking, a query is a request for information; thus, a query of the Connectivity Map aims to reveal signatures that are very similar or very different (strongly positively or negatively connected) to an input signature. The input is a list of genes. The query asks Cmap to compute connectivity scores for all instances with respect to a specified signature or a number of selected instances.
qc_f_logp The -log10 of p-value (for f statistic), representing the goodness of fit of the power model used to convert raw fluorescence intensity values to log2 expression values during the LISS process.
qc_iqr The interquartile range of normalized expression within a level 3 profile.
qc_slope The line slope in degrees (arctan of slope) of the line of best fit through the observed invariant set expression levels and their expected expression ranks.
Reduced representation of transcriptome A concept that, since genes with similar expression levels tend to have similar cellular functions or roles, the cellular state can be captured by measuring only a portion of the ~22k human genes
Replicate recall A measurement of the degree with which a signature generated by RNA-seq and used to query L1000 data finds its L1000 counterpart amidst all other RNA-seq and L1000 profiles.
Roast CMap-specific name assigned to the first four steps of the espresso computational pipeline. The Roast steps 1) deconvolute the two peaks from each bead scan and assign each peak to a particular landmark gene, 2) normalize the data by first scaling it to the invariant gene set and then standardizing it so that all of the data from a plate is on the same scale, 3) infer the expression of approximately 10,000 non-landmark genes based on the landmark gene expression for that experiment, and 4) determine the differential expression of each landmark and inferred gene relative to vehicle controls and to that gene’s expression in each of the other wells on that assay plate.
rna_plate Name of the plate as it was used throughout the assay prior to detection; the name includes all information except the bead_batch_id suffix, for example: LJP005_A375_24H_X1.
rna_well Name of a well within an rna_plate.
SSF Specialized Service Facility; this name applies to a Broad program such as CMap that provides a service for outside groups to use for their research.
Seedolog shRNAs that target different genes but share the same seed sequence, a 2-8 nucleotide sequence that contributes to off-target effects.
Signature We refer to a signature as the entire vector of differential expression values, one per gene, obtained after aggregating the data across replicates; therefore “signature” is used to refer to level 5 data (each replicate prior to aggregation is referred to as a “profile”). Signatures provide a representation of the biological response of the genome to the perturbation. For the L1000 assay, each signature is designated by its sig_id identification tag.
Signature concordance (SC) the reproducibility of gene expression changes in a signature across biological replicates.
Signature strength (SS) the number of significantly differentially expressed transcripts in a signature
Summly Given a set of connectivity scores for a particular perturbagen in several cell lines, summly is a computational method that summarizes those scores across the cell lines, resulting in a single summary score.
sig_id A CMap unique identification number assigned to each signature generated from L1000 data.
sm_center_compound_id synonym for pert_mfc_id
sm_dose synonym for pert_dose.
sm_dose_unit synonym for pert_dose_unit.
sm_lincs_id synonym for pert_id.
sm_name synonym for pert_iname.
sm_pert_type synonym for pert_type.
sm_time synonym for pert_time.
sm_time_unit synonym for pert_time_unit
Tag-duo CMap lab methodology for detecting two genes using the same analyte color.
Touchstone dataset Our reference dataset produced from a set of ~8000 perturbagens for which we have annotated biological function information, and which we have assayed in the majority of the nine core cell lines under our standard conditions.
Transcriptional activity score (TAS) TAS is a metric that incorporates the signature strength (the number of significantly differentially expressed transcripts) and signature concordance (the reproducibility of those changes across biological replicates) to capture activity of a compound. The score is computed as the geometric mean of the signature strength and the 75th quantile of pairwise replicate correlations for a given signature. Prior to computing the geometric mean, the signature strength is multiplied by the square root of the number of replicates. This serves to mitigate score shrinkage with increasing replicate number and allows TAS values derived from signatures of different numbers of replicates to be compared with each other.
Treatment dose The amount of perturbagen used to treat cells in an experiment. While dose may vary depending on the experiment, typical treatment doses range from 0.04µM to 10µM.
Treatment duration The amount of time cells are exposed to a particular perturbagen in an experiment, prior to cell lysis. Typically cells are treated with compound perturbagens for 6 hrs and 24 hrs. RNAi perturbation treatment lasts for 96 hrs.
t-SNE A dimensionality reduction technique particularly well suited for visualizing data. (For references, see https://lvdmaaten.github.io/tsne/)
target_seq The sequence within a gene that is targeted by a hairpin shRNA for knockdown, to abolish expression of that gene. This term applies to shRNA experiments only.
tas_q75 Aggregated transcriptional activity score. For a given perturbagen, tas_q75 is computed as the 75th quantile of its TAS across cell lines. The higher the number, the more generally active the perturbagen. Only exemplar signatures are used for computing tas_q75. See is_exemplar for more details.
ts_pc The percent of total Touchstone perturbagens that connect to the given perturbagen above the indicated thresholds
Z-score For a data point, the number of standard deviations that point is above or below the population mean is called its Z-score. In the L1000 data processing pipeline, we compute a robust z-score for each gene in each sample. The reference population used to compute the median and MAD is the expression of the given gene in every other well on the plate. These z-score values correspond to level 4 data.
zmad_ref The reference population used for Z scoring; generally population or vehicle, but it could be custom (see provenance code for what was used).