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Alvarez MJ, Subramaniam PS, Tang LH, Grunn A, Aburi M, Rieckhof G, Komissarova EV, Hagan EA, Bodei L, Clemons PA, Cruz FSDela, Dhall D, Diolaiti D, Fraker DA, Ghavami A, Kaemmerer D, Karan C, Kidd M, Kim KM, Kim HC, Kunju LP, Langel Ü, Li Z, Lee J, Li H, LiVolsi V, Pfragner R, Rainey AR, Realubit RB, Remotti H, Regberg J, Roses R, Rustgi A, Sepulveda AR, Serra S, Shi C, Yuan X, Barberis M, Bergamaschi R, Chinnaiyan AM, Detre T, Ezzat S, Frilling A, Hommann M, Jaeger D, Kim MK, Knudsen BS, Kung AL, Leahy E, Metz DC, Milsom JW, Park YS, Reidy-Lagunes D, Schreiber S, Washington K, Wiedenmann B, Modlin I, Califano A.  2018.  A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors.. Nat Genet. Go to Pubmed

HTS
Research scientist Hai Li holds up a 384-well plate, pictured in front of Columbia Genome Center's Hamilton Star automation system for HTS; Image credit: Systems Biology

Drug screening and analysis is critical in advancing research and discovery of cancer therapeutics. To this end, a Systems Biology-led team of investigators has recently developed PLATE-Seq, a new technique for low-cost, bulk mRNA sequencing. Coupled with genome-wide regulatory network analysis, the novel PLATE-Seq method advances the goal of providing cancer patients with personalized treatment.

Developed by the labs of Peter Sims and Andrea Califano , PLATE-Seq stands for “pooled library amplification for transcriptome expression” sequencing, and enables genome-wide mRNA profiling specifically designed to complement high-throughput screening assays. High-throughput screening, or HTS, represents a key component of drug discovery and technology used widely in biomedical research. Due to cost or complexity, most screens are still performed using low-complexity reporters, such as cell viability, protein-protein interactions and cell growth, for example, but there is a growing need to couple this screening protocol with genome-wide reporters, to measure the activity of many proteins across the genome.

“Our PLATE-Seq method helps us generate a more comprehensive portrait of drug activity,” said Dr. Sims, assistant professor of systems biology, known for his innovative work in single-cell RNA sequencing. “We’ve been able to show that our technique cuts the cost for gene expression profiling considerably, by incorporating a method we devised for ‘barcoding’ cDNA samples and combining this with computational methods from the Califano Lab that are highly effective on low-coverage sequencing data. This method allows us to sequence 96 samples per plate and 768 samples per sequencing run.”

On average, PLATE-Seq reduces the cost of genome-wide screening from around $400 per sample down to approximately $25 per sample. Genome-wide sequencing is important in advancing our understanding and prediction of disease and in identifying potential treatments.

Faculty

Laura Landweber

Professor, Biochemistry and Molecular Biophysics, and Biological Sciences

Professor, Biochemistry and Molecular Biophysics, and Biological Sciences

Faculty

Guy Sella

Affiliate Member, Program for Mathematical Genomics
Affiliate Member, Program for Mathematical Genomics

Faculty

Molly Przeworski

Professor, Department of Biological Sciences

Professor, Department of Biological Sciences

Faculty

Tuuli Lappalainen

Associate Professor, Department of Systems Biology
Core Member, New York Genome Center

Associate Professor, Department of Systems Biology
Core Member, New York Genome Center

Faculty

Chaolin Zhang

Associate Professor, Department of Systems Biology
Associate Professor, Department of Systems Biology

Faculty

Chris Wiggins

Affiliate Member, Program for Mathematical Genomics
Affiliate Member, Program for Mathematical Genomics

Faculty

Dennis Vitkup

Associate Professor, Department of Systems Biology
Associate Professor, Department of Systems Biology

Faculty

Saeed Tavazoie

Professor, Department of Biological Sciences and Systems Biology (in Biochemistry and Molecular Biophysics)
Professor, Department of Biological Sciences and Systems Biology (in Biochemistry and Molecular Biophysics)

Faculty

Nicholas Tatonetti

Associate Professor of Biomedical Informatics (in Systems Biology and in Medicine)

Associate Professor of Biomedical Informatics (in Systems Biology and in Medicine)

Faculty

Gustavo Stolovitzky

Adjunct Professor, Department of Biomedical Informatics

Adjunct Professor, Department of Biomedical Informatics

Faculty

Yufeng Shen

Associate Professor, Department of Systems Biology
Associate Director, Columbia Genome Center
Associate Professor, Department of Systems Biology
Associate Director, Columbia Genome Center

Faculty

Raul Rabadan

Gerald and Janet Carrus Professor
Professor, Department of Systems Biology

Co-director, Next-Generation Sequencing

Faculty

Itsik Pe'er

Associate Professor, Department of Computer Science

Associate Professor, Department of Computer Science

Faculty

Barry Honig

Director, Center for Computational Biology & Bioinformatics
Director, Center for Computational Biology & Bioinformatics

Faculty

Aris Floratos

Executive Research Director, Center for Computational Biology and Bioinformatics
Executive Research Director, Center for Computational Biology and Bioinformatics

Faculty

Harmen Bussemaker

Chair, Department of Biological Sciences

Chair, Department of Biological Sciences

Faculty

Dimitris Anastassiou

Charles Batchelor Professor of Electrical Engineering
Charles Batchelor Professor of Electrical Engineering

Faculty

Andrea Califano

Chair, Department of Systems Biology Clyde and Helen Wu Professor of Chemical and Systems Biology
Chair, Department of Systems Biology Clyde and Helen Wu Professor of Chemical and Systems Biology