Smita Krishnaswamy

Assistant Professor of Genetics and Computer Science
Room / Office: Watson 104
Office Address:
51 Prospect Street
New Haven, CT 06511
Mailing Address:
P.O. Box 208005
New Haven, CT 06520
Phone: (203) 785-7833
  • Ph.D., University of Michigan
  • M.S., University of Michigan
  • B.A., Kalamazoo College, Mathematics
  • B.S., University of Michigan


Smita Krishnaswamy was trained as a computer scientist with a Ph.D. from the University of Michigan's EECS department where her research focused on algorithms for automated synthesis and verification of nanoscale logic circuits that exhibit probabilistic effects. During her Ph.D., she received a best paper award at DATE 2005 (a top conference in the field of design automation), and an outstanding dissertation award. She published numerous first-author papers on probabilistic network models and algorithms for VLSICAD. In addition, her dissertation was published as a book by Springer in 2013. Following her Ph.D., she joined IBM's TJ Watson Research Center as a scientist in the systems division, where she focused on formal methods for automated error detection. Her Deltasyn algorithm was eventually utilized in IBMs p and z series high-performance chips. She then switched her research efforts to biology. Her postdoctoral training was completed at Columbia University in the systems biology department where she focused on learning computational models of cellular signaling from single-cell mass cytometry data.

Although technologies such as mass cytometry, and single-cell RNA sequencing, are able to generate high-dimensional high-throughput single-cell data, the computational, modeling and visualization techniques needed to analyze and make sense of this data are still lacking. Smita's research addresses this challenge by developing scalable computational methods for analyzing and learning predictive network models from massive biological datasets. Her methods for characterizing interactions in cellular signaling networks, published in a recent Science paper, reveal the computation performed by cells as they process signals in terms of stochastic response functions. Smita, along with experimental collaborators, have applied these methods to T cell signaling and have found that signaling response functions are reconfigured through differentiation and disease. For example, Smita and her collaborators found that subtle alterations in receptor-proximal signaling in non-obese diabetic (NOD) mice are amplified through signaling cascades leading to larger defects in downstream signals responsible for damping immune response. Her ongoing work involves creating more sophisticated and accurate models of transformational biological processes by combining both single-cell signaling and genomic data. At Yale, she is creating a forward-looking and interdisciplinary research group that is focused on developing computational techniques to solve today's challenging biological and medical problems.

Selected Publications:

  • Mingueneau M, Krishnaswamy S, Spitzer MH, Bendall SC, Stone EL, Hedrick SM, Pe'er D, Mathis D, Nolan GP, Benoist C. Single-cell mass cytometry of TCR signaling: amplification of small initial differences results in low ERK activation in NOD mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111:16466-71. 2014.
  • Amir el-AD, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, Shenfeld DK, Krishnaswamy S, Nolan GP, Pe'er D. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nature Biotechnology 2013, 31:545-52. 2013.
  • Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GP. Systems biology. Conditional density-based analysis of T cell signaling in single-cell data. Science (New York, N.Y.) 2014, 346:1250689. 2014.
  • Zunder ER, Finck R, Behbehani GK, Amir el-AD, Krishnaswamy S, Gonzalez VD, Lorang CG, Bjornson Z, Spitzer MH, Bodenmiller B, Fantl WJ, Pe'er D, Nolan GP. Palladium-based mass tag cell barcoding with a doublet-filtering scheme and single-cell deconvolution algorithm. Nature Protocols 2015, 10:316-33. 2015.
  • Smita Krishnaswamy, Igor L. Markov, John P. Hayes Lecture Notes in Electrical Engineering, Springer DOI:10.1007/978-90-481-9644-9 2013