David McCandlish
Associate Professor
Cancer Center Member
Ph.D., Duke University, 2012
[email protected] | 516-367-5286
Some mutations are harmful but others are benign. How can we predict the effects of mutations, both singly and in combination? Using data from experiments that simultaneously measure the effects of thousands of mutations, I develop computational tools to predict the functional impact of mutations and apply these tools to problems in protein design, molecular evolution, and cancer.
The McCandlish lab develops computational and mathematical tools to analyze and exploit data from high-throughput functional assays. The current focus of the lab is on analyzing data from so-called 鈥渄eep mutational scanning鈥 experiments. These experiments simultaneously determine, for a single protein, the functional effects of thousands of mutations. By aggregating information across the proteins assayed using this technique, we seek to develop data-driven insights into basic protein biology, improved models of molecular evolution, and more accurate methods for predicting the functional effects of mutations in human genome sequences.
Critically, these data also show that the functional effects of mutations often depend on which other mutations are present in the sequence. We are developing new techniques in statistics and machine learning to infer and interpret the complex patterns of genetic interaction observed in these experiments. Our ultimate goal is to be able to model these sequence-function relationships with sufficient accuracy to guide the construction of a new generation of designed enzymes and drugs, and to be able to predict the evolution of drug resistance phenotypes in both populations of cancer cells and rapidly evolving microbial pathogens.
Branching out: Tomato genes point to new medicines
July 9, 2025
Why are some vines straight and others branched? CSHL鈥檚 answer could help scientists fine-tune plant breeding techniques and clinical therapeutics.
In nature鈥檚 math, freedoms are fundamental
May 28, 2025
CSHL quantitative biologists have developed a unified theory that could have countless applications, from plant breeding to drug discovery.
You say genome editing, I say natural mutation
October 19, 2023
CSHL scientists have discovered that evolution and genome editing in crops are less predictable than previously thought.
How evolved is your knowledge?
January 26, 2023
Test your knowledge of evolution with this quiz, inspired by the March 2023 performances of Isabella Rossellini鈥檚 play, Darwin鈥檚 Smile, at CSHL.
Getting a step ahead of TB鈥檚 drug resistance evolution
February 15, 2022
Mutations are not random, with some kinds of changes occurring more often than others. CSHL researchers may be able to predict which direction evolution is li
Calculating the path of cancer
October 4, 2021
A new mathematical approach is helping cancer researchers at CSHL determine how mutations lead to different behaviors in cancerous cells.
How to outwit evolution
July 21, 2021
CSHL Assistant Professor David McCandlish uses statistical methods to predict the evolution of antibiotic resistance in bacteria.
Predicting the evolution of genetic mutations
April 14, 2020
CSHL quantitative biologists have designed a computational approach for predicting the evolution of a rapidly mutating virus or cancer.
A science career path: David McCandlish
April 10, 2020
Assistant Professor David McCandlish is a quantitative biologist who walks the line between advanced mathematics and the life sciences at CSHL.
Peter Koo wants to understand how machines learn biology
September 20, 2019
Dr. Peter Koo joins the CSHL faculty as an assistant professor. His focus is on exploring how artificial intelligence integrates with biology and genomics.
All Publications
19 Aug 2025 | bioRxiv
Zhou, Juannan; Martí-Gómez, Carlos; Petti, Samantha; McCandlish, David;
19 Jul 2025 | Nucleic Acids Research (NAR) | 53(14)
Sokirniy, Ivan; Inam, Haider; Tomaszkiewicz, Marta; Reynolds, Joshua; McCandlish, David; Pritchard, Justin;
On learning functions over biological sequence space: relating Gaussian process priors, regularization, and gauge fixing
11 Jul 2025
Petti, Samantha; Martí-Gómez, Carlos; Kinney, Justin; Zhou, Juannan; McCandlish, David;
9 Jul 2025 | Nature
Zebell, Sophia; Martí-Gómez, Carlos; Fitzgerald, Blaine; Cunha, Camila; Lach, Michael; Seman, Brooke; Hendelman, Anat; Sretenovic, Simon; Qi, Yiping; Bartlett, Madelaine; Eshed, Yuval; McCandlish, David; Lippman, Zachary;
27 Jun 2025 | bioRxiv
Sun, Mengyi; McCandlish, David;
30 Apr 2025 | bioRxiv
Petti, Samantha; Martí-Gómez, Carlos; Kinney, Justin; Zhou, Juannan; McCandlish, David;
15 Apr 2025 | Genome Biology | 26(1):97
Livesey, Benjamin; Badonyi, Mihaly; Dias, Mafalda; Frazer, Jonathan; Kumar, Sushant; Lindorff-Larsen, Kresten; McCandlish, David; Orenbuch, Rose; Shearer, Courtney; Muffley, Lara; Foreman, Julia; Glazer, Andrew; Lehner, Ben; Marks, Debora; Roth, Frederick; Rubin, Alan; Starita, Lea; Marsh, Joseph;
10 Apr 2025 | Protein Science | 32(12):101262
Avizemer, Ziv; Martí-Gómez, Carlos; Hoch, Shlomo; McCandlish, David; Fleishman, Sarel;
1 Apr 2025 | Physical Review Research | 7(2)
Posfai, A; McCandlish, D; Kinney, J;
20 Mar 2025 | PLoS Computational Biology | 21(3):e1012818
Posfai, Anna; Zhou, Juannan; McCandlish, David; Kinney, Justin; Patil, Kiran;