Ay Lab

Ay Lab

“We look beyond the linear sequence of DNA to understand how the three-dimensional architecture of the genomes influences a wide range of biological processes from the malignant transformation of cancer cells to the life cycle of the deadly malaria parasite.” — Ferhat Ay, Ph.D. // Institute Leadership Assistant Professor of Computational Biology
Division of Vaccine Discovery


The focus of Dr. Ay’s work is to understand gene regulation in complex organisms and diseases by developing novel methods that leverage high-throughput genomics and epigenomics data. He develops computational methods that are based in statistics, machine learning, optimization and graph theory. He is particularly interested in the analysis and modeling of the 3D genome architecture from high-throughput chromatin conformation capture data to understand how do changes in this 3D architecture affect cellular outcome such as development, differentiation, gene expression and disease phenotypes. He is also interested in uncovering epigenetic mechanisms behind precise regulation of gene expression in the deadly malaria parasite Plasmodium falciparum during its sexual and asexual life cycles. He also has ongoing interests in systems level analysis and reconstruction of regulatory networks, inference of enhancer-promoter contacts, predictive models of gene expression and integration of chromatin conformation data sets with one-dimensional measurements such as histone modifications, nucleosome occupancy and DNA accessibility.

From The Lab

Jan 14, 2016

La Jolla Institute welcomes new faculty member

Ay Lab


PacBio assembly of a Plasmodium knowlesi genome sequence with Hi-C correction and manual annotation of the SICAvar gene family

SA Lapp, JA Geraldo, J-T CHIEN, F Ay, SB Pakala, G Batugedara, J Humphrey, JD DeBARRY, KG Le Roch, MR Galinski, JC…

Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria

Galinski MR, Lapp SA, Peterson MS, Ay F, Joyner CJ, LE Roch KG, Fonseca LL, Voit EO; MAHPIC CONSORTIUM

Form and function of topologically associating genomic domains in budding yeast

Esera U, Chandler-Brown D, Ay F, Straight AF, Duang Z, Stafford Noble W, Skotheim JM
Nature Communications

17q21 asthma-risk variants switch CTCF binding and regulate IL-2 production by T cells.

Schmiedel BJ, Seumois G, Samaniego-Castruita D, (...) Sette A, Peters B, Vijayanand P*.
PLoS Genet

Neocentromeres provide chromosome segregation accuracy and centromere clustering to multiple loci along a candida albicans chromosome

Burrack LS, Hutton HF, Matter KJ, Clancey SA, Liachko I, Plemmons AE, Saha A, Power EA, Turman B, Thevandavakkam MA, Ay…
Genome Biol

A multitask graph-clustering approach for chomosome conformation capture data sets identifies conserved modules of chromosomal interactions

Fotuhi Siahpirani A, Ay F, Roy S
Nucleic Acids Res

A predictive modeling approach for cell line-specific long-range regulatory interactions

Roy S, Siahpirani AF, Chasman D, Knaak S, Ay F, Stewart R, Wilson M, Sridharan R
Nature Methods

Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes

W. Ma, F. Ay, C. Lee, G. Gulsoy, X. Deng, S. Cook, J. Hesson, C. Cavanaugh, CB. Ware, A. Krumm, J. Shendure, CA. Blau,…

Multiple dimensions of epigenetic gene regulation in the malaria parasite Plasmodium falciparum

F. Ay, EM. Bunnik, N. Varoquax, JP. Vert, WS. Noble, KG. Le Roch
Genome Biology

Analysis methods for studying the 3D architecture of the genome

F. Ay, WS. Noble
Genome Biology

Bipartite structure of the inactive mouse X chromosome

X. Deng, W. Ma, V. Rmani, A. Hill, F. Yang, F. Ay, JB. Berletch, CA. Blau, J. Shendure, WS. Noble, CM. Disteche
Genome Research

Comprehensive identification and analysis of human accelerated regulatory DNA

RM. Gittelman, E. Hun, F. Ay, J. Madeoy, L. Pennacchio, WS. Noble, RD. Hawkins, JM. Akey
Genome Research

Topologically-associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication timing program

V. Dileep, F. Ay, J. Sima, DL. Vera, WS. Noble, DM. Gilbert
Nucleic Acids Research

Accurate identification of centromere locations in yeast genomes using Hi-C

N. Varoquaux, I. Liachko, F. Ay, JN. Burton, J. Shendure, MJ. Dunham, JP. Vert, WS. Noble
Genome Research

Joint annotation of chromatin state and chromatin conformation reveals relationships among domain types and identifies domains of cell type-specific expression

MW. Libbrecht, F. Ay, MM. Hoffman, DM. Gilbert, JA. Bilmes, WS. Noble
BMC Genomics

Identifying multi-locus chromatin contacts in human cells using tethered multiple 3C

F. Ay, TH. Vu, MJ. Zeitz, N. Varoquax, JE. Carette, JP. Vert, AR. Hoffman, WS. Noble
Genome Research

Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression.

F. Ay*, E. M. Bunnik*, N. Varoquaux*, S. M. Bol, J. Prudhomme, J.-P. Vert, W. S. Noble and K. G. Le Roch.
Genome Research

Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts

F. Ay, T. L. Bailey and W. S. Noble.

A statistical approach for inferring the 3D structure of the genome.

N. Varoquaux, F. Ay, J.-P. Vert and W. S. Noble

Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome.

M. J. Zeitz, P. L. Lerner, F. Ay , E. V. Nostrand, J. D. Heidmann, W. S. Noble and A. R. Ho man.

Genomic interaction profiles in breast cancer reveal altered chromatin architecture.

M. J. Zeitz, F. Ay , J. D. Heidmann, P. L. Lerner, W. S. Noble, B. N. Steelman and A. R. Ho man.
Genome Research

Predictive regulatory models in Drosophila Melanogaster by integrative inference of transcriptional networks.

D. Marbach, S. Roy, F. Ay, P. Meyer, R. Candeias, T. Kahveci, C. Bristow and M. Kellis.
BMC Bioinformatics

Metabolic Network Alignment in Large Scale by Network Compression.

F. Ay, M. Dang and T. Kahveci
Journal of Computational Biology (JCB)

SubMAP: Aligning metabolic pathways with subnetwork mappings.

F. Ay, M. Kellis and T. Kahveci.

Identification of functional elements and regulatory circuits by Drosophila modENCODE

The modENCODE Consortium, S. Roy*, J. Ernst*, P.V. Kharchenko*, P. Kheradpour*, N. Negre*, M.L. Eaton*, J.M. Landolin*,…

Scalable steady state analysis of Boolean biological regulatory networks.

F. Ay, F. Xu, and T. Kahveci.
Journal of Bioinformatics and Computational Biology (JBCB)

A fast and accurate algorithm for comparative analysis of metabolic pathways

F. Ay, T. Kahveci, and V. de Crecy-Lagard.

Principal Investigator

Ferhat Ay, Ph.D.

Institute Leadership Assistant Professor of Computational Biology

Dr. Ay joined the joined the La Jolla Institute for Allergy and Immunology as Institute Leadership Assistant Professor of Computational Biology in the Division of Vaccine Discovery, in 2016. His research focuses on understanding the relationship between genome architecture and the regulation of gene activity in the malaria parasite Plasmodium falciparum as well as related issues concerning genome architecture in different organisms and in human cells, such as breast cancer and leukemia cells.

Born and raised in Turkey, Dr. Ay received a dual B.S. in computer engineering and mathematics from the Middle East Technical University in Ankara, Turkey. As part of his doctoral thesis at the University of Florida in Gainesville, he developed efficient algorithms to comparatively analyze genome-wide networks that govern metabolic activity and gene regulation in multiple organisms including the fruit fly D. melanogaster. His studies revealed that the fruit fly genome regulates its genes in a transcriptional hierarchy with extensive post-transcriptional feedback.

In recognition of his graduate work, which had revealed novel and unexpected topological patterns and relationships between different metabolic and gene regulatory networks, Dr. Ay was named- Computing Innovation Fellow by the Computing Research Association. This extremely competitive fellowship matched him with Dr. William Noble’s laboratory in the Department of Genome Sciences at the University of Washington, Seattle, where he turned his attention to the influence of the genome’s three-dimensional architecture on gene activity.

His trailblazing work provided the first evidence that the 3D configuration of DNA in the nucleus acts as a major gene regulatory mechanism in the most lethal form of malaria, Plasmodium falciparum. By providing fundamental insight into the regulatory mechanisms controlling the infectious cycle of Plasmodium, he paved the way for the development of novel lines of defense against malaria.

Before joining the La Jolla Institute as an Assistant Professor of Computational Biology, Ay worked as a Research Assistant Professor in the Department of Preventive Medicine-Health and Biomedical Informatics at Northwestern University in Chicago, IL.

Lab Members

Sourya Bhattacharyya

Bioinformatics Postdoctoral Fellow

I did the masters (M.S.) and Ph.D from the department of Computer Science and Engineering, Indian Institute of Technology Kharagpur, India. My PhD research was based on algorithms in Computational Phylogenetics, especially constructing species trees from topologically incongruent gene trees. During masters, I have worked on neonatal EEG signal and video processing for epileptic seizure detection. I joined LJI in April 2017.

Research Focus:
Developement of computational algorithms for analyzing NGS data, especially Hi-C, HiChIP, and ChIP-seq.

Career goals:
Being a computer scientist, I want to understand NGS data and genome regulation for different diseases, and work on the development of their computational models.

Abhijit Chakraborty

Postdoctoral Fellow

I did my graduation in Microbiology from India with a B.Sc degree in 2007 followed by an M.Sc degree in the same the subject in 2009. I then qualified the National Eligibility Test (NET) conducted by Council of Scientific and Industrial Research (CSIR), Govt. of India in 2009 and joined CSIR-Indian Institute of Chemical Biology in 2010 to carry out my Ph.D. research in computational biology. I successfully completed the tenure and obtained the degree in May, 2016.

Research Focus:
I began working as a postdoctoral fellow in Dr. Ay’s lab from May 2016. Here, my research focuses on understanding the gene regulation and diseases from high-throughput genomics and epigenomics data. I am interested in developing methods to understand these high-throughput data especially the chromosome conformational capture techniques like the Hi-C data. Further, I am also interested in developing 3D models of genomes using the chromosome conformational capture techniques.

Career Goal:
My goal is to pursue a career in scientific research focused on understanding the gene regulation and diseases in human.

Arya Kaul


I am an undergraduate at UC San Diego majoring in Bioengineering: Bioinformatics. I am currently interested in studying open problems in biology while utilizing theoretical mathematics and advanced computing.

Research Focus:
My research in Dr. Ay’s lab deals with utilizing Hi-C datasets to inform scaffolding during de novo genome assembly. I am also building an efficient tool to normalize Hi-C data.

Career Goals:
I wish to eventually pursue a PhD in Bioinformatics and to lead a lab centered around answering a biological question with computational rigor.

Jose Moreno


Bharat Panwar

Postdoctoral Fellow

Lucas Patel


I am an undergraduate at UCSD studying biology with specification in bioinformatics.

Research Focus:

My research under Dr. Ay at the La Jolla Institute is focused on next generation sequencing and analysis of Hi-C data. I am interested in the application of bioinformatics methods to develop solutions for medical problems.

Career Goals:
I plan to pursue a career in medicine, ideally as a physician, but I am intrigued by non-patient care career prospects as well.

Aarthi Venkat


Ay Lab

Research Projects

FIT-HI-C: Statistical Confidence Estimation for HI-C Data

Fit-Hi-C is a tool for assigning statistical confidence estimates to intra-chromosomal contact maps produced by genome-wide genome architecture assays such as Hi-C.

Project Link

Selected References

Ay, Ferhat, Timothy L. Bailey, and William Stafford Noble. "Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts." Genome research 24.6 (2014): 999-1011.

P. Falciparum 3D Genome Organization

Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression.

Project Link

Selected References

Ay, Ferhat, et al. "Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression." Genome research 24.6 (2014): 974-988.

P. Falciparum Epigenetic Gene Regulation

The third dimension of epigenetic gene regulation in the malaria parasite Plasmodium falciparum.

Project Link


ACM Conference on Bioinformatics, Computational Biology, and Health Informatics (ACM BCB), 2015

The field of regulatory genomics has recently witnessed significantly increased interest in the three-dimensional structure of DNA in the nucleus, catalyzed by the availability of chromosome conformation capture (3C) data sets that characterize the 3D organization of chromatin at a genome-wide scale. This organization, also referred to as the 3D nucleome, is not only important for packing the genome into the nucleus but also has significant impact on how the genome functions. In this tutorial, we will present recent tools and methodologies developed for analysis of genome-wide 3C data sets generated using high-throughput sequencing (Hi-C). We will cover computational approaches that span: (i) processing basics and normalization of Hi-C data, (ii) identification of genomic domains with high contact intensity, (iii) extraction of significant contacts, and (iv) inference of 3D models of the chromatin organization from contact count data. This tutorial will be beneficial for researchers in the broad fields of computational systems biology, gene regulation and transcription, next generation sequencing data analysis, and biological network modeling and analysis.

Project Link

Selected References

Ay, Ferhat, and William S. Noble. "Analysis methods for studying the 3D architecture of the genome." Genome biology 16.1 (2015): 1.

Epigenomics Session at PSB 2013

Epigenomics Session. Pacific Symposium on Biocomputing 2013

Project Link