The Library of Integrative Network-based Cellular Signatures (LINCS) was an NIH Common Fund program that lasted for 10 years from 2012-2021. The idea behind the LINCS program was to perturb different types of human cells with many different types of perturbations such as drugs and other small molecules, genetic manipulations such as single gene knockdown, knockout, or overexpression, manipulation of the extracellular microenvironment conditions, for example, growing cells on different surfaces, and more. These perturbations are applied to various types of human cells including cancer cell lines or induced pluripotent stem cells (iPSCs) from patients, differentiated into various lineages such as neurons or cardiomyocytes. Then, to better understand the molecular networks that are affected by these perturbations, changes in levels of many different molecules within the human cells were measured including: mRNAs, proteins, and metabolites, as well as cellular phenotypic changes such as cell morphology. The BD2K-LINCS Data Coordination and Integration Center (DCIC) was commissioned to organize, analyze, visualize, and integrate this data with other publicly available relevant resources. In this course, we introduce the LINCS DCIC and the various Data and Signature Generation Centers (DSGCs) that collected data for LINCS. We then cover the LINCS metadata, and how the metadata is linked to ontologies and dictionaries. We then present the data processing and data normalization methods used to clean and harmonize the LINCS data. This follows by discussions about how the LINCS data is served with RESTful APIs. Most importantly, the course covers computational bioinformatics methods that can be applied to other multi-omics datasets and projects including dimensionality reduction, clustering, gene-set enrichment analysis, interactive data visualization, and supervised learning. Finally, we introduce crowdsourcing/citizen-science projects where students can work together in teams to extract gene expression signatures from public databases, and then query such collections of signatures against the LINCS data for predicting small molecules as potential therapeutics for a collection of complex human diseases.
This module provides an overview of the concept behind the LINCS program; and tutorials on how to get started with using the LINCS L1000 dataset.
What's included
8 videos2 readings1 discussion prompt
Show info about module content
8 videos•Total 78 minutes
Layers of Cellular Regulation and Omics Technologies•7 minutes
The Connectivity Map•9 minutes
Geometrical View of the Connectivity Map Concept•4 minutes
LINCS Data and Signature Generation Centers•13 minutes
BD2K-LINCS Data Coordination and Integration Center•5 minutes
Induced Pluripotent Stem Cells (iPSCs)•5 minutes
Introduction to LINCS L1000 Data•23 minutes
L1000 Characteristic Direction Signature Search Engine (L1000CDS2) Demo•14 minutes
2 readings•Total 20 minutes
Syllabus•10 minutes
Grading and Logistics•10 minutes
1 discussion prompt•Total 10 minutes
LINCS L1000 Data - Practice Exercise•10 minutes
Metadata and Ontologies
Module 2•26 minutes to complete
Module details
This module includes a broad high level description of the concepts behind metadata and ontologies and how these are applied to LINCS datasets.
What's included
2 videos
Show info about module content
2 videos•Total 26 minutes
Introduction to Metadata and Ontologies | Part 1•5 minutes
Introduction to Metadata and Ontologies | Part 2•20 minutes
Serving Data with APIs
Module 3•29 minutes to complete
Module details
In this module we explain the concept of accessing data through an application programming interface (API).
What's included
2 videos1 discussion prompt
Show info about module content
2 videos•Total 19 minutes
Accessing and Serving Data through RESTful APIs | Part 1•8 minutes
Accessing and Serving Data through RESTful APIs | Part 2•10 minutes
1 discussion prompt•Total 10 minutes
Accessing Data through the Harmonizome's RESTful API - Practice Exercise•10 minutes
Bioinformatics Pipelines
Module 4•24 minutes to complete
Module details
This module describes the important concept of a Bioinformatics pipeline.
What's included
1 video1 discussion prompt
Show info about module content
1 video•Total 14 minutes
Analyzing Big Data with Computational Pipelines•14 minutes
1 discussion prompt•Total 10 minutes
Bioinformatics Pipeline - Practice Exercise•10 minutes
The Harmonizome
Module 5•1 hour to complete
Module details
This module describes a project that integrates many resources that contain knowledge about genes and proteins. The project is called the Harmonizome, and it is implemented as a web-server application available at: http://amp.pharm.mssm.edu/Harmonizome/
What's included
4 videos1 discussion prompt
Show info about module content
4 videos•Total 37 minutes
The Harmonizome Concept•11 minutes
Processing Datasets | Part 1•8 minutes
Processing Datasets | Part 2•9 minutes
Processing Datasets | Part 3•8 minutes
1 discussion prompt•Total 10 minutes
Harmonizome - Practice Exercise•10 minutes
Data Normalization
Module 6•29 minutes to complete
Module details
This module describes the mathematical concepts behind data normalization.
What's included
2 videos1 discussion prompt
Show info about module content
2 videos•Total 19 minutes
Data Normalization | Part 1•6 minutes
Data Normalization | Part 2•13 minutes
1 discussion prompt•Total 10 minutes
Data Normalization - Practice Exercise•10 minutes
Data Clustering
Module 7•1 hour to complete
Module details
This module describes the mathematical concepts behind data clustering, or in other words unsupervised learning - the identification of patterns within data without considering the labels associated with the data.
What's included
3 videos1 discussion prompt
Show info about module content
3 videos•Total 33 minutes
Data Clustering | Part 1 | Introduction•5 minutes
Data Clustering | Part 2 | Distance Functions •12 minutes
Data Clustering | Part 3 | Algorithms and Evaluation•16 minutes
1 discussion prompt•Total 10 minutes
Data Clustering - Practice Exercise•10 minutes
Midterm Exam
Module 8•1 hour to complete
Module details
The Midterm Exam consists of 45 multiple choice questions which covers modules 1-7. Some of the questions may require you to perform some analysis with the methods you learned throughout the course on new datasets.
What's included
1 assignment
Show info about module content
1 assignment•Total 30 minutes
Midterm Exam•30 minutes
Enrichment Analysis
Module 9•29 minutes to complete
Module details
This module introduces the important concept of performing gene set enrichment analyses. Enrichment analysis is the process of querying gene sets from genomics and proteomics studies against annotated gene sets collected from prior biological knowledge.
What's included
3 videos
Show info about module content
3 videos•Total 29 minutes
Enrichment Analysis | Part 1•12 minutes
Enrichment Analysis | Part 2•7 minutes
Enrichr Demo•10 minutes
Machine Learning
Module 10•1 hour to complete
Module details
This module describes the mathematical concepts of supervised machine learning, the process of making predictions from examples that associate observations/features/attribute with one or more properties that we wish to learn/predict.
What's included
3 videos1 discussion prompt
Show info about module content
3 videos•Total 27 minutes
Introduction to Machine Learning | Part 1•9 minutes
Introduction to Machine Learning | Part 2 •8 minutes
Introduction to Machine Learning | Part 3•10 minutes
1 discussion prompt•Total 10 minutes
Machine Learning - Practice Exercise•10 minutes
Benchmarking
Module 11•26 minutes to complete
Module details
This module discusses how Bioinformatics pipelines can be compared and evaluated.
What's included
2 videos1 discussion prompt
Show info about module content
2 videos•Total 16 minutes
Benchmarking | Part 1•6 minutes
Benchmarking | Part 2•10 minutes
1 discussion prompt•Total 10 minutes
Benchmarking - Practice Exercise•10 minutes
Interactive Data Visualization
Module 12•1 hour to complete
Module details
This module provides programming examples on how to get started with creating interactive web-based data visualization elements/figures.
What's included
4 videos1 discussion prompt
Show info about module content
4 videos•Total 69 minutes
Interactive Data Visualization with E-Charts•22 minutes
Visualizing Data using Interactive Clustergrams Built with D3.js | Part 1•18 minutes
Visualizing Data using Interactive Clustergrams Built with D3.js | Part 2•11 minutes
Visualizing Data using Interactive Clustergrams Built with D3.js | Part 3•18 minutes
1 discussion prompt•Total 10 minutes
Visualizing Gene Expression Data using Interactive Clustergrams Built with D3.js - Practice Exercise•10 minutes
Crowdsourcing Projects
Module 13•19 minutes to complete
Module details
This final module describes opportunities to work on LINCS related projects that go beyond the course.
What's included
2 videos1 reading
Show info about module content
2 videos•Total 9 minutes
Microtasks and GEO2Enrichr Demo•4 minutes
L1000-2-P100 Megatask Challenge•4 minutes
1 reading•Total 10 minutes
BD2K-LINCS DCIC Crowdsourcing Portal•10 minutes
Final Exam
Module 14•1 hour to complete
Module details
The Final Exam consists of 60 multiple choice questions which covers all of the modules of the course. Some of the questions may require you to perform some analysis with the methods you learned throughout the course on new datasets.
What's included
1 assignment
Show info about module content
1 assignment•Total 30 minutes
Final Exam•30 minutes
Instructor
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Instructor ratings
We asked all learners to give feedback on our instructors based on the quality of their teaching style.
The Icahn School of Medicine at Mount Sinai, in New York City is a leader in medical and scientific training and education, biomedical research and patient care.
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