Scholars@Duke
Raluca Mihaela Gordan

Raluca Mihaela Gordan

Adjunct Associate Professor in the Department of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Integrative Genomics
raluca.gordan@duke.edu
Duke Box 3382, Durham, NC 27710
101 Science Drive, 2179 CIEMAS, Durham, NC 27708

Selected Publications

The epigenetic landscape shapes smoking-induced mutagenesis by modulating DNA damage susceptibility and repair efficiency.

Journal Article Nucleic Acids Res · February 8, 2025 Lung cancer sequencing efforts have uncovered mutational signatures that are attributed to exposure to the cigarette smoke carcinogen benzo[a]pyrene. Benzo[a]pyrene metabolizes in cells to benzo[a]pyrene diol epoxide (BPDE) and reacts with guanine nucleoti ... Full text Link to item Cite

High UV damage and low repair, but not cytosine deamination, stimulate mutation hotspots at ETS binding sites in melanoma.

Journal Article Proc Natl Acad Sci U S A · January 23, 2024 Noncoding mutation hotspots have been identified in melanoma and many of them occur at the binding sites of E26 transformation-specific (ETS) proteins; however, their formation mechanism and functional impacts are not fully understood. Here, we used UV (Ul ... Full text Link to item Cite

High-throughput data and modeling reveal insights into the mechanisms of cooperative DNA-binding by transcription factor proteins.

Journal Article Nucleic Acids Res · November 27, 2023 Cooperative DNA-binding by transcription factor (TF) proteins is critical for eukaryotic gene regulation. In the human genome, many regulatory regions contain TF-binding sites in close proximity to each other, which can facilitate cooperative interactions. ... Full text Link to item Cite

Short tandem repeats bind transcription factors to tune eukaryotic gene expression.

Journal Article Science · September 22, 2023 Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by abo ... Full text Link to item Cite

Computational design of sequence-specific DNA-binding proteins.

Journal Article bioRxiv · September 21, 2023 Sequence-specific DNA-binding proteins (DBPs) play critical roles in biology and biotechnology, and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has ... Full text Link to item Cite

UV irradiation remodels the specificity landscape of transcription factors.

Journal Article Proc Natl Acad Sci U S A · March 14, 2023 Somatic mutations are highly enriched at transcription factor (TF) binding sites, with the strongest trend being observed for ultraviolet light (UV)-induced mutations in melanomas. One of the main mechanisms proposed for this hypermutation pattern is the i ... Full text Link to item Cite

MESH1 knockdown triggers proliferation arrest through TAZ repression.

Journal Article Cell Death Dis · March 10, 2022 All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main stress-coping mechanism is the stringent response triggered by the accumulation of "alarmone" (p)ppGpp to arrest proliferation a ... Full text Link to item Cite

Transcription Factor-Centric Approach to Identify Non-recurring Putative Regulatory Drivers in Cancer

Conference Lecture Notes in Computer Science Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics · January 1, 2022 Recent efforts to sequence the genomes of thousands of matched normal-tumor samples have led to the identification of millions of somatic mutations, the majority of which are non-coding. Most of these mutations are believed to be passengers, but a small nu ... Full text Cite

Sex dependent glial-specific changes in the chromatin accessibility landscape in late-onset Alzheimer's disease brains.

Journal Article Mol Neurodegener · August 24, 2021 BACKGROUND: In the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer's disease (LOAD) and translate the associations to causation. METHODS: We conducted ATAC-seq profiling using NeuN sorted-nuclei f ... Full text Link to item Cite

Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions.

Journal Article Genome Res · July 2021 Most eukaryotic transcription factors (TFs) are part of large protein families, with members of the same family (i.e., paralogous TFs) recognizing similar DNA-binding motifs but performing different regulatory functions. Many TF paralogs are coexpressed in ... Full text Link to item Cite

Mutational processes in cancer preferentially affect binding of particular transcription factors.

Journal Article Sci Rep · February 8, 2021 Protein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial ... Full text Open Access Link to item Cite

DNA mismatches reveal conformational penalties in protein-DNA recognition.

Journal Article Nature · November 2020 Transcription factors recognize specific genomic sequences to regulate complex gene-expression programs. Although it is well-established that transcription factors bind to specific DNA sequences using a combination of base readout and shape recognition, so ... Full text Open Access Link to item Cite

DNA Sequence Recognition by DNA Primase Using High-Throughput Primase Profiling.

Journal Article J Vis Exp · October 8, 2019 DNA primase synthesizes short RNA primers that initiate DNA synthesis of Okazaki fragments on the lagging strand by DNA polymerase during DNA replication. The binding of prokaryotic DnaG-like primases to DNA occurs at a specific trinucleotide recognition s ... Full text Link to item Cite

Unexpected implications of STAT3 acetylation revealed by genetic encoding of acetyl-lysine.

Journal Article Biochim Biophys Acta Gen Subj · September 2019 The signal transducer and activator of transcription 3 (STAT3) protein is activated by phosphorylation of a specific tyrosine residue (Tyr705) in response to various extracellular signals. STAT3 activity was also found to be regulated by acetylation of Lys ... Full text Link to item Cite

QBiC-Pred: quantitative predictions of transcription factor binding changes due to sequence variants.

Journal Article Nucleic Acids Res · July 2, 2019 Non-coding genetic variants/mutations can play functional roles in the cell by disrupting regulatory interactions between transcription factors (TFs) and their genomic target sites. For most human TFs, a myriad of DNA-binding models are available and could ... Full text Link to item Cite

Genetic variation determines VEGF-A plasma levels in cancer patients.

Journal Article Sci Rep · November 5, 2018 Angiogenesis is essential in tumor biology and is regulated by vascular endothelial growth factor (VEGF) ligands and receptors. Here we aimed to discover genetic variants associated with levels of circulating angiogenic proteins in cancer patients. Plasma ... Full text Link to item Cite

Toward deciphering the mechanistic role of variations in the Rep1 repeat site in the transcription regulation of SNCA gene.

Journal Article Neurogenetics · August 2018 Short structural variants-variants other than single nucleotide polymorphisms-are hypothesized to contribute to many complex diseases, possibly by modulating gene expression. However, the molecular mechanisms by which noncoding short structural variants ex ... Full text Link to item Cite

The Vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation

Journal Article Plos One · August 1, 2018 Purpose Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) i ... Full text Cite

DNA Sequence Context Controls the Binding and Processivity of the T7 DNA Primase

Journal Article Iscience · April 27, 2018 Primases are key enzymes involved in DNA replication. They act on single-stranded DNA and catalyze the synthesis of short RNA primers used by DNA polymerases. Here, we investigate the DNA binding and activity of the bacteriophage T7 primase using a new wor ... Full text Cite

Divergence in DNA Specificity among Paralogous Transcription Factors Contributes to Their Differential In Vivo Binding.

Journal Article Cell Syst · April 25, 2018 Paralogous transcription factors (TFs) are oftentimes reported to have identical DNA-binding motifs, despite the fact that they perform distinct regulatory functions. Differential genomic targeting by paralogous TFs is generally assumed to be due to intera ... Full text Link to item Cite

Incomplete MyoD-induced transdifferentiation is associated with chromatin remodeling deficiencies.

Journal Article Nucleic Acids Res · November 16, 2017 Our current understanding of cellular transdifferentiation systems is limited. It is oftentimes unknown, at a genome-wide scale, how much transdifferentiated cells differ quantitatively from both the starting cells and the target cells. Focusing on transdi ... Full text Link to item Cite

Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.

Journal Article Cancer Discov · October 2017 Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and D ... Full text Link to item Cite

Inkjet-printed point-of-care immunoassay on a nanoscale polymer brush enables subpicomolar detection of analytes in blood.

Journal Article Proc Natl Acad Sci U S A · August 22, 2017 The ELISA is the mainstay for sensitive and quantitative detection of protein analytes. Despite its utility, ELISA is time-consuming, resource-intensive, and infrastructure-dependent, limiting its availability in resource-limited regions. Here, we describe ... Full text Link to item Cite

Quantifying the Impact of Non-coding Variants on Transcription Factor-DNA Binding.

Conference Res Comput Mol Biol · May 2017 Many recent studies have emphasized the importance of genetic variants and mutations in cancer and other complex human diseases. The overwhelming majority of these variants occur in non-coding portions of the genome, where they can have a functional impact ... Full text Link to item Cite

Expression level is a key determinant of E2F1-mediated cell fate.

Journal Article Cell Death Differ · April 2017 The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both ... Full text Link to item Cite

Establishment of Expression in the SHORTROOT-SCARECROW Transcriptional Cascade through Opposing Activities of Both Activators and Repressors.

Journal Article Dev Cell · December 5, 2016 Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However, it is unclear how expression is established at the top of these cascades in the absence of pre-existing specificity. We generated a trans ... Full text Link to item Cite

Transcription Factor-DNA Binding Motifs in Saccharomyces cerevisiae: Tools and Resources.

Journal Article Cold Spring Harb Protoc · November 1, 2016 The DNA binding specificity of transcription factors (TFs) is typically represented in the form of a position weight matrix (PWM), also known as a DNA motif. A PWM is a matrix that specifies, for each position in the DNA binding site of a TF, the "weight" ... Full text Link to item Cite

Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi.

Journal Article Elife · May 10, 2016 Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuate ... Full text Open Access Link to item Cite

Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi

Journal Article Elife · May 10, 2016 Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuate ... Full text Open Access Cite

Survey of variation in human transcription factors reveals prevalent DNA binding changes.

Journal Article Science · March 25, 2016 Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based ap ... Full text Link to item Cite

HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells.

Journal Article Epigenetics Chromatin · 2016 BACKGROUND: Small molecule inhibitors of histone deacetylases (HDACi) hold promise as anticancer agents for particular malignancies. However, clinical use is often confounded by toxicity, perhaps due to indiscriminate hyperacetylation of cellular proteins. ... Full text Open Access Link to item Cite

Nonconsensus Protein Binding to Repetitive DNA Sequence Elements Significantly Affects Eukaryotic Genomes.

Journal Article PLoS Comput Biol · August 2015 Recent genome-wide experiments in different eukaryotic genomes provide an unprecedented view of transcription factor (TF) binding locations and of nucleosome occupancy. These experiments revealed that a large fraction of TF binding events occur in regions ... Full text Link to item Cite

Quantitative modeling of transcription factor binding specificities using DNA shape.

Journal Article Proc Natl Acad Sci U S A · April 14, 2015 DNA binding specificities of transcription factors (TFs) are a key component of gene regulatory processes. Underlying mechanisms that explain the highly specific binding of TFs to their genomic target sites are poorly understood. A better understanding of ... Full text Link to item Cite

Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex.

Journal Article Curr Biol · March 16, 2015 The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctive ... Full text Open Access Link to item Cite

Protein-DNA binding in the absence of specific base-pair recognition.

Journal Article Proc Natl Acad Sci U S A · December 2, 2014 Until now, it has been reasonably assumed that specific base-pair recognition is the only mechanism controlling the specificity of transcription factor (TF)-DNA binding. Contrary to this assumption, here we show that nonspecific DNA sequences possessing ce ... Full text Link to item Cite

Absence of a simple code: how transcription factors read the genome.

Journal Article Trends Biochem Sci · September 2014 Transcription factors (TFs) influence cell fate by interpreting the regulatory DNA within a genome. TFs recognize DNA in a specific manner; the mechanisms underlying this specificity have been identified for many TFs based on 3D structures of protein-DNA c ... Full text Link to item Cite

COUGER--co-factors associated with uniquely-bound genomic regions.

Journal Article Nucleic Acids Res · July 2014 Most transcription factors (TFs) belong to protein families that share a common DNA binding domain and have very similar DNA binding preferences. However, many paralogous TFs (i.e. members of the same TF family) perform different regulatory functions and i ... Full text Link to item Cite

Protein-DNA binding: complexities and multi-protein codes.

Journal Article Nucleic Acids Res · February 2014 Binding of proteins to particular DNA sites across the genome is a primary determinant of specificity in genome maintenance and gene regulation. DNA-binding specificity is encoded at multiple levels, from the detailed biophysical interactions between prote ... Full text Link to item Cite

TFBSshape: a motif database for DNA shape features of transcription factor binding sites.

Journal Article Nucleic Acids Res · January 2014 Transcription factor binding sites (TFBSs) are most commonly characterized by the nucleotide preferences at each position of the DNA target. Whereas these sequence motifs are quite accurate descriptions of DNA binding specificities of transcription factors ... Full text Link to item Cite

Sequence specificity incompletely defines the genome-wide occupancy of Myc.

Journal Article Genome Biol · 2014 BACKGROUND: The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements, CACGTG or variants, to which the heterodimer binds ... Full text Link to item Cite

Stability selection for regression-based models of transcription factor-DNA binding specificity.

Journal Article Bioinformatics · July 1, 2013 MOTIVATION: The DNA binding specificity of a transcription factor (TF) is typically represented using a position weight matrix model, which implicitly assumes that individual bases in a TF binding site contribute independently to the binding affinity, an a ... Full text Open Access Link to item Cite

Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape.

Journal Article Cell Rep · April 25, 2013 DNA sequence is a major determinant of the binding specificity of transcription factors (TFs) for their genomic targets. However, eukaryotic cells often express, at the same time, TFs with highly similar DNA binding motifs but distinct in vivo targets. Cur ... Full text Link to item Cite

Distinguishing between genomic regions bound by paralogous transcription factors

Journal Article Lecture Notes in Computer Science Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics · April 3, 2013 Transcription factors (TFs) regulate gene expression by binding to specific DNA sites in cis regulatory regions of genes. Most eukaryotic TFs are members of protein families that share a common DNA binding domain and often recognize highly similar DNA sequ ... Full text Cite

Identification of cell cycle-regulated, putative hyphal genes in Candida albicans.

Journal Article Pac Symp Biocomput · 2012 Candida albicans, a major fungal pathogen in human, can grow in a variety of morphological forms ranging from budding yeast to pseudohyphae and hyphae, and its ability to transition to true hyphae is critical for virulence in various types of C. albicans i ... Link to item Cite

Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights.

Journal Article Genome Biol · December 21, 2011 BACKGROUND: Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding specificities of most Saccharomyces c ... Full text Link to item Cite

Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing.

Journal Article RNA · April 2011 Tat specific factor 1 (Tat-SF1) interacts with components of both the transcription and splicing machineries and has been classified as a transcription-splicing factor. Although its function as an HIV-1 dependency factor has been investigated, relatively l ... Full text Link to item Cite

Finding regulatory DNA motifs using alignment-free evolutionary conservation information.

Journal Article Nucleic Acids Res · April 2010 As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery ... Full text Open Access Link to item Cite

Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading.

Journal Article Genome Res · February 2010 The origin recognition complex (ORC) is an essential DNA replication initiation factor conserved in all eukaryotes. In Saccharomyces cerevisiae, ORC binds to specific DNA elements; however, in higher eukaryotes, ORC exhibits little sequence specificity in ... Full text Link to item Cite

Finding regulatory DNA motifs using alignment-free evolutionary conservation information

Journal Article Nucleic Acids Research · January 4, 2010 As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery ... Full text Cite

Distinguishing direct versus indirect transcription factor-DNA interactions.

Journal Article Genome Res · November 2009 Transcriptional regulation is largely enacted by transcription factors (TFs) binding DNA. Large numbers of TF binding motifs have been revealed by ChIP-chip experiments followed by computational DNA motif discovery. However, the success of motif discovery ... Full text Link to item Cite

Using DNA duplex stability information for transcription factor binding site discovery.

Conference Pac Symp Biocomput · 2008 Transcription factor (TF) binding site discovery is an important step in understanding transcriptional regulation. Many computational tools have already been developed, but their success in detecting TF motifs is still limited. We believe one of the main r ... Link to item Cite

A nucleosome-guided map of transcription factor binding sites in yeast.

Journal Article PLoS Comput Biol · November 2007 Finding functional DNA binding sites of transcription factors (TFs) throughout the genome is a crucial step in understanding transcriptional regulation. Unfortunately, these binding sites are typically short and degenerate, posing a significant statistical ... Full text Open Access Link to item Cite

Informative priors based on transcription factor structural class improve de novo motif discovery.

Journal Article Bioinformatics · July 15, 2006 MOTIVATION: An important problem in molecular biology is to identify the locations at which a transcription factor (TF) binds to DNA, given a set of DNA sequences believed to be bound by that TF. In previous work, we showed that information in the DNA sequ ... Full text Link to item Cite