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

Overview

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

Publications

Genome Biology

A multi-task graph-clustering approach for chromosome conformation capture data sets identifies conserved modules of chromosomal interactions

2016-05
AF Siahpirani, F Ay, S Roy
Nucleic Acids Res

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

2016-02
S Roy, AF Siahpirani, D Chasman, S Knaak, F Ay, R Stewart, M Wilson, R Sridharan
Genome Biology

Analysis methods for studying the 3D architecture of the genom

2015-09
F. Ay, WS. Noble
Genome Biology

Bipartite structure of the inactive mouse X chromosome

2015-08
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

2015-09
RM. Gittelman, E. Hun, F. Ay, J. Madeoy, L. Pennacchio, WS. Noble, RD. Hawkins, JM. Akey
Nucleic Acids Research

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

2015-11
S. Roy, AF. Siahpirani, D. Chasman, S. Knaack, F. Ay, R. Stewart, M. Wilson, R. Sridharan
Genome Research

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

2015-08
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

2015-06
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

2015-04
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

2015-02
F. Ay, TH. Vu, MJ. Zeitz, N. Varoquax, JE. Carette, JP. Vert, AR. Hoffman, WS. Noble
Nature Methods

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

2015-01
W. Ma, F. Ay, C. Lee, G. Gulsoy, X. Deng, S. Cook, J. Hesson, C. Cavanaugh, CB. Ware, A. Krumm, J. Shendure, CA. Blau,…
Bioessays

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

2015-02
F. Ay, EM. Bunnik, N. Varoquax, JP. Vert, WS. Noble, KG. Le Roch
Bioinformatics

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

2014-06
N. Varoquaux, F. Ay, WS. Noble, JP. Vert
Genome Research

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

2014-03
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 con dence estimation for Hi-C data reveals regulatory chromatin contacts

2014-06
F. Ay, T. L. Bailey and W. S. Noble.
Bioinformatics

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

2014-06
N. Varoquaux, F. Ay, J.-P. Vert and W. S. Noble
Nucleus

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

2013-12
M. J. Zeitz, P. L. Lerner, F. Ay , E. V. Nostrand, J. D. Heidmann, W. S. Noble and A. R. Ho man.
PLoS ONE

Genomic interaction pro les in breast cancer reveal altered chromatin architecture.

2013-09
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.

2012-07
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.

2012-03
F. Ay, M. Dang and T. Kahveci
Journal of Computational Biology (JCB)

SubMAP: Aligning metabolic pathways with subnetwork mappings.

2011-03
F. Ay, M. Kellis and T. Kahveci.
Science

Identification of functional elements and regulatory circuits by Drosophila modENCODE

2010-12
The modENCODE Consortium, S. Roy*, J. Ernst*, P.V. Kharchenko*, P. Kheradpour*, N. Negre*, M.L. Eaton*, J.M. Landolin*,…
PLoS ONE

Scalable steady state analysis of Boolean biological regulatory networks.

2009-12
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

2009-06
F. Ay, T. Kahveci, and V. de Crecy-Lagard.

Principal Investigator

ay

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

AbhijitChakraborty2

Abhijit Chakraborty

Postdoctoral Fellow

Biosketch:
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

Intern

Lucas.Patel

Lucas Patel

Intern

Biosketch:
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.

Rohan Paul

Intern

AishaniChittorPrem

Aishani Chittoor Prem

Intern

Biosketch:
I completed my Bachelors in Biotechnology in the year 2014 from Jawaharlala Nehru Technology University, India. I am currently a Master’s student at San Diego State University in Bioinformatics. I started working in Ay lab at La Jolla Institute of Allergy and Immunology in March 2016 as a Bioinformatics Intern.

Research Focus:
My current research project is focused on modeling and analysis of three-dimensional genome structure of high-throughput chromatin conformation capture data (Hi-C data) and to understand the affects of these 3D structure on gene expression.

Career Goals:
My plan is to develop a career in the research field as a bioinformatics scientist.

Jianlin Shao, PhD

Postdoctoral Fellow

Ruyu Tan

Ruyu Tan

Intern

Biosketch:
I graduated from Lanzhou University, China in 2015 with a B.S. degree in Mathematics. I am currently a master student at University of California, San Diego in statistics. I started working in Ay Lab at the La Jolla Institute for Allergy and Immunology in June 2016 as an internship.

Research Focus:
My research projects are focused on the high-throughput chromatin conformation capture data (Hi-C data) and the software Fit-Hi- C, also extending it to programming language R. I am interested in application the methods and models in statistics to biology.

Career Goal:
My plan is to pursue a career in scientific research focused on biostatistics.

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

TUTORIAL AT ACM-BCB 2015

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