LSP Data and Methods

The t-CyCIF method builds on earlier methods involving repeated staining and imaging to generate multiplexed images of formalin-fixed, paraffin-embedded (FFPE) samples using an iterative process (a cycle) in which conventional low-plex fluorescence images are repeatedly collected from the same sample and then assembled into a high dimensional representation. Highly multiplexed images of intact tumor architecture can be used to quantify signal transduction cascades, measure the levels of tumor antigens and determine immunophenotypes using immune cell lineage markers. t-CyCIF is a powerful tool to study drug resistance of immunotherapy in different patients.

Reliable high-throughput imaging of cells grown in multi-plate wells is complicated by the loss of cells during staining and wash steps. The dye drop method uses a set of incrementally more dense solutions to prevent cell loss. Dye Drop software consists of Python tools for determining the viability and cell cycle states of cells before and after drug treatment.

The Growth Rate inhibition (GR) Calculator (grcalculator.org) is an open source set of Python, R and online tools for quantifying the responses of cancer cells to drugs in a manner that corrects for the confounding effects of variable cell proliferation rates. Response metrics computed from GR data include GR50 and GRmax and are direct analogs of familiar IC50 and Emax response measures.

The HMS LINCS Database is a public resource for browsing, searching, and downloading all fully annotated datasets generated through the HMS LINCS Center along with experimental and analytical methods. The database contains >350 datasets from imaging, transcriptomic, and proteomic experiments as well as in vitro small molecule affinity assays.

The Harvard Tissue Atlas (HTA) gathers together image and omic datasets into molecular maps. Our atlases bring together multiple research projects examining normal and diseased tissue from human and animal models, with an emphasis on cancer. The goal of these atlases is to describe the myriad of interactions that occur between cells and acellular structures within tissues to advance our understanding of disease initiation and progression. This will help develop a new generation of diagnostic molecular tests, which are needed for disease stratification in clinical trials and precision medicine for patients. 

ProteinNet is a standardized data set for machine learning of protein structure. It provides protein sequences, structures (secondary and tertiary), multiple sequence alignments (MSAs), position-specific scoring matrices (PSSMs), and standardized training / validation / test splits. ProteinNet builds on the biennial CASP assessments, which carry out blind predictions of recently solved but publicly unavailable protein structures, to provide test sets that push the frontiers of computational methodology. It is organized as a series of data sets, spanning CASP 7 through 12 (covering a ten-year period), to provide a range of data set sizes that enable the assessment of new methods in relatively data-poor and data-rich regimes.

DRIAD (Drug Repurposing In Alzheimer’s Disease) is a machine learning framework for identifying potential associations between Alzheimer’s Disease pathology and individual genes. DRIAD was applied to data from perturbation experiments performed in the LSP using differentiated human neural cell cultures and 80 FDA-approved and clinically tested drugs, to nominate existing drugs that could be potentially be repurposed for Alzheimer’s treatment. 

CancerTrials.io contains imputed individual participant data (IPD) from previously published oncology research clinical trials (RCTs). The site also contains various types of analysis performed on these data.

DUB (Deubiquitinating enzymes) portal provides the integration and analysis of publicly available resources as well as newly collected transcriptomic data following DUB knockout or inhibition to facilitate the exploration of DUB function in oncology.