Article
Biochemical Research Methods
Christopher S. Juerges, Lars Doelken, Florian Erhard
Summary: The study introduces a comprehensive approach called iTiSS for accurately identifying TSS in any eukaryotic TSS profiling experiment, reducing false positives by jointly analyzing multiple complementary datasets.
Article
Biochemical Research Methods
Dania Machlab, Lukas Burger, Charlotte Soneson, Filippo M. Rijli, Dirk Schuebeler, Michael B. Stadler
Summary: Proteins binding to specific nucleotide sequences, such as transcription factors, have significant roles in regulating gene expression. The monaLisa package, an R/Bioconductor package, provides methods to identify relevant transcription factors from experimental data. It allows seamless motif analyses without relying on software outside of R.
Article
Biochemistry & Molecular Biology
Eugeniya I. Bondar, Maxim E. Troukhan, Konstantin V. Krutovsky, Tatiana V. Tatarinova
Summary: This study utilized computational approaches to predict genome-wide TSS in four conifer species, laying the groundwork for future research on gene regulatory regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Microbiology
Thi Tuong Vi Dang, Jessie Colin, Guilhem Janbon
Summary: Pathogenic fungi require delicate gene regulation mechanisms to adapt and survive in different environments. The usage of alternative transcription start sites (aTSS) in fungi plays a crucial role in fine-tuning gene expression, and disrupted control of aTSS can severely affect fungal growth and infectious capacity.
Article
Biochemistry & Molecular Biology
Matthew Dyer, Quy Xiao Xuan Lin, Sofiia Shapoval, Denis Thieffry, Touati Benoukraf
Summary: MethMotif is a publicly available database that provides a comprehensive repository of transcription factor-binding profiles with DNA methylation patterns. The latest release includes over 700 position weight matrices, segregated based on their cofactors and DNA methylation status. The database also offers precomputed GO annotations for human TFs and TF-co-TF complexes, allowing for a comprehensive analysis of TF functions in their context with cofactors. Furthermore, MethMotif has been expanded to include data for two additional species, increasing its applicability and value to the scientific community.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Olga A. Nikolaitchik, Saiful Islam, Jonathan P. Kitzrow, Alice Duchon, Zetao Cheng, Yang Liu, Jonathan M. O. Rawson, Wei Shao, Maria Nikolaitchik, Mary F. Kearney, Frank Maldarelli, Karin Musier-Forsyth, Vinay K. Pathak, Wei-Shau Hu, Malcolm Martin
Summary: HIV-1 uses host RNA polymerase II (Pol II) to transcribe its genome and employs multiple transcription start sites (TSS). Selection of TSS is regulated by specific sequences near the TATA box and R. Mutants expressing specific RNA transcripts with different numbers of guanosines at the 5'-end exhibit replication defects compared to the wild-type. These findings highlight the importance of TSS selection for HIV-1 replication fitness and genome integrity during reverse transcription.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Inna A. Suvorova, Mikhail S. Gelfand
Summary: Comparative genomics techniques were used to identify binding motifs of IclR-family TFs, reconstruct regulons, and analyze their content. Two main types of IclR-family motifs were described, with possible alternative modes of dimerization, as well as trends in site positioning and protein-DNA contacts. The majority of predicted protein-DNA contacts were similar for both types of motifs and aligned well with available experimental data and general protein-DNA interaction trends.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eric J. Tomko, Olivia Luyties, Jenna K. Rimel, Chi-Lin Tsai, Jill O. Fuss, James Fishburn, Steven Hahn, Susan E. Tsutakawa, Dylan J. Taatjes, Eric A. Galburt
Summary: The general transcription factor TFIIH contains three ATP-dependent catalytic activities and functions in nucleotide excision repair and Pol II transcription initiation. While the functions are conserved between metazoans and yeast, yeast TFIIH drives transcription start-site scanning. Human and yeast core-TFIIH complexes lack processive translocation, with the yeast kinase module aiding in robust transcription start-site scanning.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Sarah M. Morgan, Hideki Tanizawa, Lisa Beatrice Caruso, Michael Hulse, Andrew Kossenkov, Jozef Madzo, Kelsey Keith, Yinfei Tan, Sarah Boyle, Paul M. Lieberman, Italo Tempera
Summary: This study demonstrates the essential role of PARP1 in regulating the chromatin structure and gene expression of EBV. PARP inhibition leads to decreased intragenomic interactions within the EBV episome, but also forms new chromatin loops. Additionally, PARP inhibition alters the binding of chromatin looping factor CTCF and gene expression.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Dimitris Grigoriadis, Nikos Perdikopanis, Georgios K. Georgakilas, Artemis G. Hatzigeorgiou
Summary: This study presents DeepTSS, a novel computational method for processing CAGE samples, that combines genomic signal processing (GSP), DNA features, evolutionary conservation evidence and Deep Learning (DL) to provide accurate TSS predictions. Experimental results show that DeepTSS outperforms existing algorithms on all benchmarks.
BMC BIOINFORMATICS
(2022)
Article
Computer Science, Artificial Intelligence
Jose A. Barbero-Aparicio, Alicia Olivares-Gil, Jose F. Diez-Pastor, Cesar Garcia-Osorio
Summary: Recognizing transcription start sites is crucial for gene identification. This article compares the performance of support vector machines (SVMs) and deep learning methods, specifically long short-term memory neural networks (LSTMs), in predicting transcription start sites. The results show that deep learning methods are better suited for this task, especially when working with sequence data. Additionally, a method for generating transcription start site datasets and the importance of balanced data are discussed.
PEERJ COMPUTER SCIENCE
(2023)
Article
Plant Sciences
Andrew Murray, John Pablo Mendieta, Chris Vollmers, Robert J. Schmitz
Summary: The accurate identification and quantification of transcriptional start sites (TSSs) is crucial for understanding transcription control. In this study, the researchers developed Smar2C2, a new method that allows for the easy and efficient identification of TSSs and transcription termination sites. Using this method, they were able to identify TSSs in multiple plant species and discover evolutionarily conserved features as well as sequence variations in known promoter motifs that may have significant implications for our understanding and control of transcription initiation.
Article
Biotechnology & Applied Microbiology
Hong-Leong Cheah, Siti Aminah Ahmed, Thean-Hock Tang
Summary: This study establishes the transcription start site (TSS) landscape and small RNA (sRNA) profile of L. biflexa serovar Patoc through differential RNA-seq analysis, revealing 2726 TSSs and 603 sRNAs. These findings enhance our understanding of the regulatory networks in L. biflexa.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel Marri, David Filipovic, Omar Kana, Shelley Tischkau, Sudin Bhattacharya
Summary: The Brain and Muscle ARNTL-Like 1 protein (BMAL1) forms heterodimers with CLOCK or NPAS2 to regulate circadian clock genes. Using machine learning models, we identified features that predict BMAL1-DNA binding and provided insights into tissue specificity. We found that histone modifications, DNA shape, and the flanking sequence of E-box motifs are sufficient predictive features for BMAL1-DNA binding.
SCIENTIFIC REPORTS
(2023)
Article
Plant Sciences
Huiling Cheng, Lifen Liu, Yuying Zhou, Kaixuan Deng, Yuanxin Ge, Xuehai Hu
Summary: An emerging approach using promoter tiling deletion via genome editing is becoming popular in plants. However, the precise positions of core motifs within plant gene promoters are largely unknown. In this study, the researchers developed TSPTFBS 2.0, which integrates DenseNet-based models and three interpretability methods to identify potential core motifs in genomic regions. The developed web-server has great potentials for providing reliable editing targets in genetic screen experiments in plants.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yunhui Peng, Yaroslav Markov, Alexander Goncearenco, David Landsman, Anna R. Panchenko
Summary: This study comprehensively mapped human histone interaction networks and found limited overlap between networks from different data sources. The analysis revealed scale-free behavior and high modularity of the human histone interactome, with a high number of residues involved in interactions. Additionally, two types of histone binding modes were detected.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Genetics & Heredity
Aroon T. Chande, Shashwat Deepali Nagar, Lavanya Rishishwar, Leonardo Marino-Ramirez, Miguel A. Medina-Rivas, Augusto E. Valderrama-Aguirre, I. King Jordan, Juan Esteban Gallo
Summary: The study examined the impact of different ethnic groups and genetic ancestry on disease prevalence and risk in Colombia, finding that Mestizo and Indigenous populations showed the highest correlations with disease prevalence, while Afro-Colombians had a lower impact. Additionally, African genetic ancestry was found to be most strongly correlated with predicted disease risk, while European and Native American ancestry had weaker effects. The study highlights the importance of considering both ethnicity and genetic ancestry in precision medicine development.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Shuxiang Li, Yunhui Peng, David Landsman, Anna R. Panchenko
Summary: This study investigates the effects of cytosine methylation at CpG sites on nucleosome dynamics and stability. The results show that methylation induces significant changes in the geometry of DNA, leading to enhanced interactions with the histone octamer and preventing DNA unwrapping.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Shashwat Deepali Nagar, Andrew B. Conley, Shivam Sharma, Lavanya Rishishwar, I King Jordan, Leonardo Marino-Ramirez
Summary: The study found that there are differences in CRP levels between ethnicities, with Black individuals having higher average CRP levels than White individuals, and females having higher levels than males. The associations between CRP levels, ethnicity, and genetic ancestry were almost completely attenuated after adjusting for socioenvironmental factors and health conditions.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Leonardo Marino-Ramirez, Shivam Sharma, Lavanya Rishishwar, Andrew B. Conley, Shashwat Deepali Nagar, I. King Jordan
Summary: The inclusion of ethnicity in estimating glomerular filtration rate (eGFR) from creatinine levels has been challenged. Genetic ancestry is more strongly associated with creatinine levels than self-identified ethnicity, suggesting that ethnic differences in creatinine may be shaped by genetic factors rather than social factors.
Letter
Medicine, General & Internal
Leonardo Marino-Ramirez, I. King Jordan, Anna Maria Napoles, Eliseo J. Perez-Stable
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Biochemistry & Molecular Biology
Andrew B. Conley, Lavanya Rishishwar, Maria Ahmad, Shivam Sharma, Emily T. Norris, I. King Jordan, Leonardo Marino-Ramirez
Summary: Biobank projects generate genomic data for thousands of individuals, requiring computational methods such as genetic ancestry inference tools. Current methods do not scale to biobank-sized datasets. The Rye algorithm was developed for scalable genetic ancestry inference, outperforming existing programs in accuracy and runtime performance on a dataset from the UK Biobank. Rye utilizes principal component analysis and optimization techniques to estimate genetic ancestry at both continental and subcontinental levels.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Iris Zhu, David Landsman
Summary: Housekeeping genes are regulated by cell type-specific enhancers, and most transcription factors bind cell type-specifically. TF binding at regulatory sites is cell type-specific and is related to the collective TF recruitment, as each cell type has a unique repertoire of TFs. The top TF-enriched regulatory sites in HepG2 cells can be predicted from the binding profile of as few as 30 TFs.
Article
Genetics & Heredity
I. King Jordan, Shivam Sharma, Leonardo Marino-Ramirez
Summary: Health equity means ensuring equal opportunity for everyone to achieve optimal health. In the field of pharmacogenomics, genetic differences in how patients respond to medications can inform treatment decisions. Population pharmacogenomics studies the variations within and between human populations, and it can help promote fairness in patient treatments and outcomes. Racial and ethnic groups exhibit significant differences in the frequencies of pharmacogenomic variants, which have direct implications for clinical practice.
Article
Pharmacology & Pharmacy
Shivam Sharma, Leonardo Marino-Ramirez, I. King Jordan
Summary: The relevance of race and ethnicity to genetics and medicine is debated. This study evaluated the relationship between race, ethnicity, and clinically relevant pharmacogenomic variation. The results show that pharmacogenomic variation can predict race and ethnicity, indicating their importance in treatment decisions.
Article
Mathematical & Computational Biology
Shashwat Deepali Nagar, I. King Jordan, Leonardo Marino-Ramirez
Summary: The UK Biobank (UKB) is a large-scale biomedical database that holds demographic and electronic health record data for over 500,000 participants of diverse ethnic backgrounds, which could be a valuable resource for studying health disparities. However, there are no publicly accessible databases that catalog health disparities within the UKB. To address this, we developed the UKB Health Disparities Browser to facilitate exploration of health disparities in the UK and bring attention to areas of research with significant public health impact.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2023)
Letter
Multidisciplinary Sciences
Leonardo Marino-Ramirez, Eliseo J. Perez-Stable, I. King Jordan
Article
Health Care Sciences & Services
Whitney L. Teagle, Emily T. Norris, Lavanya Rishishwar, Shashwat Deepali Nagar, I. King Jordan, Leonardo Marino-Ramirez
Summary: The objective of this study was to explore the relationship between comorbidities and ethnic health disparities. The UK Biobank was used to analyze disease prevalence and patterns of comorbidities among five ethnic groups in the UK. The results showed that the Asian group had the highest number of comorbidities, while the Chinese group had the lowest. There were significant variations in comorbidity prevalence among ethnic groups for almost all disease categories, with diabetes and hypertension showing the largest differences. These findings highlight the extent to which comorbidities vary among ethnic groups and reveal specific comorbidities that contribute to ethnic health disparities.
Article
Oncology
Kara Keun Lee, Lavanya Rishishwar, Dongjo Ban, Shashwat Deepali Nagar, Leonardo Marino-Ramirez, John F. McDonald, I. King Jordan
Article
Medicine, General & Internal
Shashwat Deepali Nagar, Anna Maria Napoles, I. King Jordan, Leonardo Marino-Ramirez
Summary: In the UK, Asian ethnic group has the highest prevalence of T2D, and both socioeconomic deprivation (SED) and non-European genetic ancestry (GA) are significantly associated with T2D disparities. There are significant interaction effects of GA and SED on T2D, with SED being a relatively greater risk factor for individuals with South Asian and African ancestry.