Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure
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Abstract
Abstract Understanding the genetic regulatory code governing gene expression is an important challenge in molecular biology. However, how individual coding and non-coding regions of the gene regulatory structure interact and contribute to mRNA expression levels remains unclear. Here we apply deep learning on over 20,000 mRNA datasets to examine the genetic regulatory code controlling mRNA abundance in 7 model organisms ranging from bacteria to Human. In all organisms, we can predict mRNA abundance directly from DNA sequence, with up to 82% of the variation of transcript levels encoded in the gene regulatory structure. By searching for DNA regulatory motifs across the gene regulatory structure, we discover that motif interactions could explain the whole dynamic range of mRNA levels. Co-evolution across coding and non-coding regions suggests that it is not single motifs or regions, but the entire gene regulatory structure and specific combination of regulatory elements that define gene expression levels.
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Deep learning has been applied and shown great performance in modelling chemical spaces, gene expression, enzyme-related parameters such as enzyme affinity and EC numbers.
“Deep learning has been applied and shown great performance in modelling chemical spaces 18 , gene expression 19 , enzyme-related parameters such as enzyme affinity 20 and EC numbers 21 .”
From Deep learning-based kcat prediction enables improved enzyme-constrained model reconstruction (2022) · cites this paper as [19]
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ImageNet classification with deep convolutional neural networks
Krizhevsky, A., Sutskever, I., & Hinton, G. E. (2017) · Communications of the ACM · doi:10.1145/3065386 · Cited by 112,155 · see citing works
Hochreiter, S., & Schmidhuber, J. (1997) · Neural Computation · doi:10.1162/neco.1997.9.8.1735 · Cited by 102,318 · see citing works
Adam: A Method for Stochastic Optimization
Kingma, D. P., & Ba, J. (2014) · arXiv · doi:10.48550/arxiv.1412.6980 · Cited by 98,946 · see citing works
Going deeper with convolutions
Szegedy, C., Liu, W., Jia, Y., Sermanet, P., Reed, S., Anguelov, D., Erhan, D., Vanhoucke, V., & Rabinovich, A. (2015) · 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) · doi:10.1109/cvpr.2015.7298594 · Cited by 48,562 · see citing works
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
Katoh, K., & Standley, D. M. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst010 · Cited by 46,209 · see citing works
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
(2014) · Cited by 33,419 · see citing works
MrBayes 3: Bayesian phylogenetic inference under mixed models
Ronquist, F., & Huelsenbeck, J. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg180 · Cited by 28,956 · see citing works
The Elements of Statistical Learning
Hastie, T., Tibshirani, R., & Friedman, J. (2009) · Springer Series in Statistics · doi:10.1007/978-0-387-84858-7 · Cited by 25,970 · see citing works
Delving Deep into Rectifiers: Surpassing Human-Level Performance on ImageNet Classification
He, K., Zhang, X., Ren, S., & Sun, J. (2015) · 2015 IEEE International Conference on Computer Vision (ICCV) · doi:10.1109/iccv.2015.123 · Cited by 19,741 · see citing works
Visualizing and understanding convolutional networks
Zeiler, M. D., & Fergus, R. (2014) · Lecture Notes in Computer Science · doi:10.1007/978-3-319-10590-1_53 · Cited by 15,839 · see citing works
Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate ShiftPreprint
Ioffe, S. (2024) · arXiv (Cornell University) · doi:10.57702/o9raffed · Cited by 15,273 · see citing works
An Analysis of Transformations
Box, G. E. P., & Cox, D. R. (1964) · Journal of the Royal Statistical Society Series B (Statistical Methodology) · doi:10.1111/j.2517-6161.1964.tb00553.x · Cited by 15,059 · see citing works
(2010) · International Conference on Machine Learning · Cited by 13,995 · see citing works
Representation Learning: A Review and New Perspectives
Bengio, Y., Courville, A., & Vincent, P. (2013) · IEEE Transactions on Pattern Analysis and Machine Intelligence · doi:10.1109/tpami.2013.50 · Cited by 13,001 · see citing works
Cd-hit: Accelerated for clustering the next-generation sequencing data
Fu, L., Niu, B., Zhu, Z., Wu, S., & Li, W. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts565 · Cited by 11,175 · see citing works
Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences
Li, W.-Z., & Godzik, A. (2006) · Bioinform. · doi:10.1093/bioinformatics/btl158 · Cited by 10,990 · see citing works
MEME SUITE: tools for motif discovery and searching
Bailey, T. L., Boden, M., Buske, F. A., Frith, M., Grant, C. E., Clementi, L., Ren, J., Li, W. W., & Noble, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp335 · Cited by 10,648 · see citing works
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Mining frequent patterns without candidate generation
Han, J., Pei, J., & Yin, Y. (2000) · ACM SIGMOD Record · doi:10.1145/335191.335372 · Cited by 6,402 · see citing works
Biopython: freely available python tools for computational molecular biology and bioinformatics
Cock, P. J. A., Antao, T., Chang, J. T., Chapman, B. A., Cox, C. J., Dalke, A., Friedberg, I., Hamelryck, T., Kauff, F., Wilczynski, B., et al. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp163 · Cited by 6,080 · see citing works
ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking
Wilkerson, M. D., & Hayes, D. N. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq170 · Cited by 5,719 · see citing works
The Gene Ontology Resource: 20 years and still GOing strong
The Gene Ontology Consortium (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1055 · Cited by 4,747 · see citing works
(2011) · Cited by 3,939 · see citing works
Tumour heterogeneity and resistance to cancer therapies
Dagogo-Jack, I., & Shaw, A. T. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.166 · Cited by 3,846 · see citing works
On the Dependency of Cellular Protein Levels on mRNA Abundance
Liu, Y., Beyer, A., & Aebersold, R. (2016) · Cell · doi:10.1016/j.cell.2016.03.014 · Cited by 3,221 · see citing works
Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning
Alipanahi, B., Delong, A., Weirauch, M. T., & Frey, B. J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3300 · Cited by 2,873 · see citing works
A survey of best practices for RNA-seq data analysis
Conesa, A., Madrigal, P., Tarazona, S., Gomez-Cabrero, D., Cervera, A., McPherson, A., Szcześniak, M. W., Gaffney, D. J., Elo, L. L., Zhang, X., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-0881-8 · Cited by 2,794 · see citing works
The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing
Nagalakshmi, U., Wang, Z., Waern, K., Shou, C., Raha, D., Gerstein, M., & Snyder, M. (2008) · Science · doi:10.1126/science.1158441 · Cited by 2,479 · see citing works
Predicting effects of noncoding variants with deep learning–based sequence model
Zhou, J., & Troyanskaya, O. G. (2015) · Nature Methods · doi:10.1038/nmeth.3547 · Cited by 2,338 · see citing works
Practical Recommendations for Gradient-Based Training of Deep Architectures
Bengio, Y. (2012) · Lecture Notes in Computer Science · doi:10.1007/978-3-642-35289-8_26 · Cited by 2,259 · see citing works
Watson, J. D. (1970) · Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) · Cited by 2,069 · see citing works
Quantifying similarity between motifs
Gupta, S., Stamatoyannopoulos, J. A., Bailey, T. L., & Noble, W. S. (2007) · Genome Biology · doi:10.1186/gb-2007-8-2-r24 · Cited by 2,058 · see citing works
Production of recombinant protein therapeutics in cultivated mammalian cells
Wurm, F. M. (2004) · Nature Biotechnology · doi:10.1038/nbt1026 · Cited by 2,032 · see citing works
AU-rich elements: characterization and importance in mRNA degradation
Chen, C.-Y. A., & Shyu, A.-B. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89102-1 · Cited by 1,948 · see citing works
Saccharomyces Genome Database: the genomics resource of budding yeast
Cherry, J., Hong, E., Amundsen, C., Balakrishnan, R., Binkley, G., Chan, E. T., Christie, K., Costanzo, M., Dwight, S., Engel, S., et al. (2011) · Nucleic Acids Res. · doi:10.1093/nar/gkr1029 · Cited by 1,886 · see citing works
Toward accurate dynamic time warping in linear time and space
Salvador, S., & Chan, P. K. (2007) · Intelligent Data Analysis · doi:10.3233/ida-2007-11508 · Cited by 1,712 · see citing works
Synonymous but not the same: the causes and consequences of codon bias
Plotkin, J. B., & Kudla, G. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2899 · Cited by 1,677 · see citing works
Khan, A., Fornés, O., Stigliani, A., Gheorghe, M., Castro-Mondragon, J. A., van der Lee, R., Bessy, A., Chèneby, J., Kulkarni, S. R., Tan, G., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1126 · Cited by 1,436 · see citing works
Saxonov, S., Berg, P., & Brutlag, D. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510310103 · Cited by 1,401 · see citing works
The elements of statistical learning: Data mining, inference, and prediction
Franklin, J. (2005) · The Mathematical Intelligencer · doi:10.1007/bf02985802 · Cited by 1,400 · see citing works
Engineering Cellular Metabolism
Nielsen, J., & Keasling, J. D. (2016) · Cell · doi:10.1016/j.cell.2016.02.004 · Cited by 1,397 · see citing works
Self-citationThe human transcriptome across tissues and individuals
Melé, M., Ferreira, P. G., Reverter, F., DeLuca, D. S., Monlong, J., Sammeth, M., Young, T. R., Goldmann, J. M., Pervouchine, D. D., Sullivan, T. J., et al. (2015) · Science · doi:10.1126/science.aaa0355 · Cited by 1,304 · see citing works
Mechanisms and Regulation of Alternative Pre-mRNA Splicing
Lee, Y., & Rio, D. C. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034316 · Cited by 1,291 · see citing works
Cis-regulatory elements: Molecular mechanisms and evolutionary processes underlying divergence
Wittkopp, P. J., & Kalay, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3095 · Cited by 1,231 · see citing works
RNA-Seq gene expression estimation with read mapping uncertainty
Li, B., Ruotti, V., Stewart, R. M., Thomson, J. A., & Dewey, C. N. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp692 · Cited by 1,198 · see citing works
SGD: Saccharomyces Genome Database
Cherry, J. M. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.73 · Cited by 1,145 · see citing works
Hershberg, R., & Petrov, D. A. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.42.110807.091442 · Cited by 1,056 · see citing works
Kelley, D. R., Snoek, J., & Rinn, J. L. (2016) · Genome Research · doi:10.1101/gr.200535.115 · Cited by 1,048 · see citing works
Hyperopt: a Python library for model selection and hyperparameter optimization
Bergstra, J., Komer, B., Eliasmith, C., Yamins, D., & Cox, D. D. (2015) · Computational Science & Discovery · doi:10.1088/1749-4699/8/1/014008 · Cited by 1,002 · see citing works
Khan, A., Fornes, O., Stigliani, A., Gheorghe, M., Castro-Mondragon, J., van der Lee, R., Bessy, A., Chèneby, J., Kulkarni, S. R., Tan, G., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1188 · Cited by 973 · see citing works
Object Recognition with Gradient-Based Learning
LeCun, Y., Haffner, P., Bottou, L., & Bengio, Y. (1999) · Lecture Notes in Computer Science · doi:10.1007/3-540-46805-6_19 · Cited by 947 · see citing works
Information content of binding sites on nucleotide sequences
Schneider, T. D., Stormo, G. D., Gold, L., & Ehrenfeucht, A. (1986) · Journal of Molecular Biology · doi:10.1016/0022-2836(86)90165-8 · Cited by 944 · see citing works
Bidirectional promoters generate pervasive transcription in yeast
Xu, Z., Wei, W., Gagneur, J., Perocchi, F., Clauder‐Münster, S., Camblong, J., Guffanti, E., Stutz, F., Huber, W. K., & Steinmetz, L. M. (2009) · Nature · doi:10.1038/nature07728 · Cited by 926 · see citing works
Cunningham, F., Achuthan, P., Akanni, W., Allen, J., Amode, M. R., Armean, I. M., Bennett, R., Bhai, J., Billis, K., Boddu, S., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1113 · Cited by 925 · see citing works
A Highly Characterized Yeast Toolkit for Modular, Multipart Assembly
Lee, M. E., DeLoache, W. C., Cervantes, B., & Dueber, J. E. (2015) · ACS Synthetic Biology · doi:10.1021/sb500366v · Cited by 874 · see citing works
Evolutionary changes in cis and trans gene regulation
Wittkopp, P. J., Haerum, B. K., & Clark, A. G. (2004) · Nature · doi:10.1038/nature02698 · Cited by 873 · see citing works
Quang, D. X., & Xie, X. S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw226 · Cited by 840 · see citing works
Furey, T. S. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3306 · Cited by 839 · see citing works
Codon optimality, bias and usage in translation and mRNA decay
Hanson, G., & Coller, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.91 · Cited by 825 · see citing works
Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world
Koonin, E. V., & Wolf, Y. I. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn668 · Cited by 793 · see citing works
Codon Bias as a Means to Fine-Tune Gene Expression
Quax, T. E. F., Claassens, N. J., Söll, D. G., & John van der, O. O. S. T. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.035 · Cited by 779 · see citing works
Towards better understanding of gradient-based attribution methods for Deep Neural NetworksPreprint
Ancona, M., Ceolini, E., Öztireli, C., & Groß, M. H. (2017) · Zurich Open Repository and Archive (University of Zurich) · doi:10.3929/ethz-b-000249929 · Cited by 634 · see citing works
van Dijken, J. P., Bauer, J., Brambilla, L., Duboc, P., Francois, J. M., Gancedo, C., Giuseppin, M. L. F., Heijnen, J. J., Hoare, M., Lange, H. C., et al. (2000) · Enzyme and Microbial Technology · doi:10.1016/s0141-0229(00)00162-9 · Cited by 598 · see citing works
Self-citationMarguerat, S., Schmidt, A., Codlin, S., Chen, W., Aebersold, R., & Bähler, J. (2012) · Cell · doi:10.1016/j.cell.2012.09.019 · Cited by 571 · see citing works
Evidence for stabilizing selection in a eukaryotic enhancer element
Ludwig, M. Z., Bergman, C., Patel, N. H., & Kreitman, M. (2000) · Nature · doi:10.1038/35000615 · Cited by 563 · see citing works
Huisinga, K. L., & Pugh, B. F. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00087-5 · Cited by 561 · see citing works
Absence of a simple code: how transcription factors read the genome
Slattery, M., Zhou, T., Yang, L., Dantas Machado, A. C., Gordân, R., & Rohs, R. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.07.002 · Cited by 537 · see citing works
Sharon, E., Kalma, Y., Sharp, A., Raveh-Sadka, T., Levo, M., Zeevi, D., Keren, L., Yakhini, Z., Weinberger, A., & Segal, E. (2012) · Nature Biotechnology · doi:10.1038/nbt.2205 · Cited by 457 · see citing works
Zhou, Z., Dang, Y., Zhou, M., Li, L., Yu, C., Fu, J., Chen, S., & Liu, Y. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606724113 · Cited by 441 · see citing works
A Yeast Hybrid Provides Insight into the Evolution of Gene Expression Regulation
Tirosh, I., Reikhav, S., Levy, A. A., & Barkai, N. (2009) · Science · doi:10.1126/science.1169766 · Cited by 399 · see citing works
Franklin, J. S. (2005) · The Mathematical Intelligencer · Cited by 392 · see citing works
Two strategies for gene regulation by promoter nucleosomesPreprint
Tirosh, I., & Barkai, N. (2008) · Genome Research · doi:10.1101/gr.076059.108 · Cited by 383 · see citing works
Codon usage between genomes is constrained by genome-wide mutational processes
Chen, S. L., Lee, W., Hottes, A. K., Shapiro, L., & McAdams, H. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307827100 · Cited by 369 · see citing works
Santos-Zavaleta, A., Salgado, H., Gama‐Castro, S., Sánchez-Pérez, M., Gómez-Romero, L., Ledezma-Tejeida, D., García-Sotelo, J. S., Alquicira‐Hernández, K., Muñiz-Rascado, L., Peña-Loredo, P., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1077 · Cited by 351 · see citing works
An empirical analysis of feature engineering for predictive modeling
Heaton, J. (2016) · SoutheastCon 2016 · doi:10.1109/secon.2016.7506650 · Cited by 301 · see citing works
Deciphering eukaryotic gene-regulatory logic with 100 million random promoters
de Boer, C. G., Vaishnav, E. D., Sadeh, R., Abeyta, E. L., Friedman, N., & Regev, A. (2020) · Nature Biotechnology · doi:10.1038/s41587-019-0315-8 · Cited by 283 · see citing works
Pierce, N. A., & Winfree, E. (2002) · Protein Engineering Design and Selection · doi:10.1093/protein/15.10.779 · Cited by 270 · see citing works
Jessop-Fabre, M. M., Jakočiūnas, T., Šťovíček, V., Dai, Z., Jensen, M. K., Keasling, J. D., & Borodina, I. (2016) · Biotechnology Journal · doi:10.1002/biot.201600147 · Cited by 270 · see citing works
Chepelev, I., Wei, G., Wangsa, D., Tang, Q., & Zhao, K. (2012) · Cell Research · doi:10.1038/cr.2012.15 · Cited by 253 · see citing works
Li, Y., Lee, K. K., Walsh, S., Smith, C., Hadingham, S., Sorefan, K., Cawley, G. C., & Bevan, M. W. (2006) · Genome Research · doi:10.1101/gr.4237406 · Cited by 251 · see citing works
Gene Expression Intensity Shapes Evolutionary Rates of the Proteins Encoded by the Vertebrate Genome
Subramanian, S., & Kumar, S. (2004) · Genetics · doi:10.1534/genetics.104.028944 · Cited by 250 · see citing works
Deciphering the rules by which 5′-UTR sequences affect protein expression in yeast
Dvir, S., Velten, L., Sharon, E., Zeevi, D., Carey, L. B., Weinberger, A., & Segal, E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222534110 · Cited by 246 · see citing works
Discriminative prediction of mammalian enhancers from DNA sequencePreprint
Lee, D., Karchin, R., & Beer, M. (2011) · Genome Research · doi:10.1101/gr.121905.111 · Cited by 245 · see citing works
Predicting mRNA abundance directly from genomic sequence using deep convolutional neural networks
Agarwal, V., & Shendure, J. (2018) · doi:10.1101/416685 · Cited by 243 · see citing works
Predicting mRNA Abundance Directly from Genomic Sequence Using Deep Convolutional Neural Networks
Agarwal, V., & Shendure, J. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107663 · Cited by 243 · see citing works
Short Synthetic Terminators for Improved Heterologous Gene Expression in Yeast
Curran, K. A., Morse, N. J., Markham, K. A., Wagman, A. M., Gupta, A. M., & Alper, H. S. (2015) · ACS Synthetic Biology · doi:10.1021/sb5003357 · Cited by 227 · see citing works
Peng, B., Williams, T. C., Henry, M. N., Nielsen, L. K., & Vickers, C. E. (2015) · Microbial Cell Factories · doi:10.1186/s12934-015-0278-5 · Cited by 213 · see citing works
Synthetic promoter libraries – tuning of gene expression
Hammer, K., Mijakovic̀, I., & Jensen, P. R. (2006) · Trends in biotechnology · doi:10.1016/j.tibtech.2005.12.003 · Cited by 207 · see citing works
Accounting For Alignment Uncertainty in Phylogenomics
Wu, M., Chatterji, S., & Eisen, J. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030288 · Cited by 206 · see citing works
Cuperus, J. T., Groves, B., Kuchina, A., Rosenberg, A. B., Jojic, N., Fields, S., & Seelig, G. (2017) · Genome Research · doi:10.1101/gr.224964.117 · Cited by 205 · see citing works
Nakagawa, S., Niimura, Y., Gojobori, T., Tanaka, H., & Miura, K.-I. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm1102 · Cited by 202 · see citing works
Promoters maintain their relative activity levels under different growth conditions
Keren, L., Zackay, O., Lotan‐Pompan, M., Barenholz, U., Dekel, E., Sasson, V., Aidelberg, G., Bren, A., Zeevi, D., Weinberger, A., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.59 · Cited by 198 · see citing works
Lahtvee, P.-J., Sánchez, B. J., Smialowska, A., Kasvandik, S., Elsemman, I. E., Gatto, F., & Nielsen, J. (2017) · Cell Systems · doi:10.1016/j.cels.2017.03.003 · Cited by 193 · see citing works
Self-citationLove, M. I., Hogenesch, J. B., & Irizarry, R. A. (2016) · Nature Biotechnology · doi:10.1038/nbt.3682 · Cited by 186 · see citing works
Teixeira, M. C., Monteiro, P. T., Palma, M., Costa, C., Godinho, C. P., Pais, P., Cavalheiro, M., Antunes, M., Lemos, A., Pedreira, T., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx842 · Cited by 182 · see citing works
Altschul, S. F., & ERICKSON, B. (1985) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040370 · Cited by 165 · see citing works
Trabelsi, A., Chaâbane, M. A., & Ben‐Hur, A. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz339 · Cited by 153 · see citing works
PhenoMeNal: processing and analysis of metabolomics data in the cloud
Peters, K., Bradbury, J., Bergmann, S., Capuccini, M., Cascante, M., de Atauri, P., Ebbels, T. M. D., Foguet, C., Glen, R. C., Gonzalez-Beltran, A. N., et al. (2018) · GigaScience · doi:10.1093/gigascience/giy149 · Cited by 151 · see citing works
Unraveling determinants of transcription factor binding outside the core binding sitePreprint
Levo, M., Zalckvar, E., Sharon, E., Machado, A. C. D., Kalma, Y., Lotan‐Pompan, M., Weinberger, A., Zohar Yakhini, B., Rohs, R., & Segal, E. (2015) · Genome Research · doi:10.1101/gr.185033.114 · Cited by 144 · see citing works
Design of synthetic yeast promoters via tuning of nucleosome architecture
Curran, K. A., Crook, N., Karim, A. S., Gupta, A. M., Wagman, A. M., & Alper, H. S. (2014) · Nature Communications · doi:10.1038/ncomms5002 · Cited by 140 · see citing works
cis -Regulatory and Protein Evolution in Orthologous and Duplicate GenesPreprint
Castillo-Davis, C. I., Hartl, D. L., & Achaz, G. (2004) · Genome Research · doi:10.1101/gr.2662504 · Cited by 134 · see citing works
The PhyloPythiaS Web Server for Taxonomic Assignment of Metagenome Sequences
Patil, K. R., Roune, L., & McHardy, A. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038581 · Cited by 133 · see citing works
Predictable tuning of protein expression in bacteria
Bonde, M., Pedersen, M., Klausen, M. S., Jensen, S. I., Wulff, T., Harrison, S. J., Nielsen, A. T., Herrgård, M. J., & Sommer, M. O. A. (2016) · Nature Methods · doi:10.1038/nmeth.3727 · Cited by 133 · see citing works
Reconstructing genetic history of Siberian and Northeastern European populationsPreprint
Wong, E. H. M., Владимирович, Х. А., Nichols, L., Pushkarev, D., Khokhrin, D. V., Анатольевич, В. Д., Evgrafov, O. V., Knowles, J. A., Novembre, J., Limborska, S., et al. (2016) · Genome Research · doi:10.1101/gr.202945.115 · Cited by 131 · see citing works
A primer to frequent itemset mining for bioinformatics
Naulaerts, S., Meysman, P., Bittremieux, W., Vu, T. N., Berghe, W. V., Goethals, B., & Laukens, K. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbt074 · Cited by 130 · see citing works
Genome-wide inference of natural selection on human transcription factor binding sites
Arbiza, L., Gronau, I., Aksoy, B. A., Hubisz, M. J., Gulko, B., Keinan, A., & Siepel, A. C. (2013) · Nature Genetics · doi:10.1038/ng.2658 · Cited by 128 · see citing works
Rabani, M., Pieper, L. M., Chew, G.-L., & Schier, A. F. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.11.014 · Cited by 125 · see citing works
Jenjaroenpun, P., Wongsurawat, T., Pereira, R., Patumcharoenpol, P., Ussery, D. W., Nielsen, J., & Nookaew, I. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky014 · Cited by 125 · see citing works
Self-citationYamanishi, M., Ito, Y., Kintaka, R., Imamura, C., Katahira, S., Ikeuchi, A., Moriya, H., & Matsuyama, T. (2013) · ACS Synthetic Biology · doi:10.1021/sb300116y · Cited by 121 · see citing works
Genomic evidence for elevated mutation rates in highly expressed genes
Park, C., Qian, W., & Zhang, J. (2012) · EMBO Reports · doi:10.1038/embor.2012.165 · Cited by 120 · see citing works
Synthetic Core Promoters as Universal Parts for Fine-Tuning Expression in Different Yeast Species
Portela, R. M. C., Vogl, T., Kniely, C., Fischer, J. E., Oliveira, R., & Glieder, A. (2016) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00178 · Cited by 117 · see citing works
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Mora, A., Sandve, G. K., Gabrielsen, O. S., & Eskeland, R. (2015) · Briefings in Bioinformatics · doi:10.1093/bib/bbv097 · Cited by 115 · see citing works
Representation learning of genomic sequence motifs with convolutional neural networks
Koo, P. K., & Eddy, S. R. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007560 · Cited by 112 · see citing works
Core promoter sequence in yeast is a major determinant of expression levelPreprint
Lubliner, S., Regev, I., Lotan-Pompan, M., Edelheit, S., Weinberger, A., & Segal, E. (2015) · Genome Research · doi:10.1101/gr.188193.114 · Cited by 111 · see citing works
Codon usage influences fitness through RNA toxicity
Mittal, P., Brindle, J., Stephen, J. O., Plotkin, J. B., & Kudla, G. R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810022115 · Cited by 107 · see citing works
Machine Learning Predicts the Yeast Metabolome from the Quantitative Proteome of Kinase Knockouts
Zelezniak, A., Vowinckel, J., Capuano, F., Messner, C. B., Demichev, V., Polowsky, N., Mülleder, M., Kamrad, S., Klaus, B., Keller, M. A., et al. (2018) · Cell Systems · doi:10.1016/j.cels.2018.08.001 · Cited by 100 · see citing works
Self-citationHiraoka, Y., Kawamata, K., Haraguchi, T., & Chikashige, Y. (2009) · Genes to Cells · doi:10.1111/j.1365-2443.2009.01284.x · Cited by 97 · see citing works
He, B., Holloway, A. K., Maerkl, S. J., & Kreitman, M. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002053 · Cited by 91 · see citing works
The metabolic background is a global player in Saccharomyces gene expression epistasis
Alam, M. T., Zelezniak, A., Mülleder, M., Shliaha, P. V., Schwarz, R. F., Capuano, F., Vowinckel, J., Radmaneshfar, E., Krüger, A., Calvani, E., et al. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2015.30 · Cited by 87 · see citing works
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Zicola, J., Liu, L., Tänzler, P., & Turck, F. (2019) · Nature Plants · doi:10.1038/s41477-019-0375-2 · Cited by 84 · see citing works
<i>Cis</i> -regulatory elements explain most of the mRNA stability variation across genes in yeast
Cheng, J., Maier, K. C., Avsec, Ž., Rus, P., & Gagneur, J. (2017) · RNA · doi:10.1261/rna.062224.117 · Cited by 79 · see citing works
Chen, Y., Pai, A. A., Herudek, J., Lubas, M., Meola, N., Järvelin, A. I., Andersson, R., Pelechano, V., Steinmetz, L. M., Jensen, T. H., et al. (2016) · Nature Genetics · doi:10.1038/ng.3616 · Cited by 78 · see citing works
Reducing mutational bias in random protein libraries
Vanhercke, T., Ampè, C., Tirry, L., & Denolf, P. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2004.11.032 · Cited by 73 · see citing works
Systematic Dissection of the Sequence Determinants of Gene 3’ End Mediated Expression Control
Shalem, O., Sharon, E., Lubliner, S., Regev, I., Lotan-Pompan, M., Yakhini, Z., & Segal, E. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005147 · Cited by 69 · see citing works
Zhou, Z., Dang, Y., Zhou, M., Yuan, H., & Liu, Y. (2018) · eLife · doi:10.7554/elife.33569 · Cited by 69 · see citing works
Digital expression explorer 2: a repository of uniformly processed RNA sequencing data
Ziemann, M., Kaspi, A., & El‐Osta, A. (2019) · GigaScience · doi:10.1093/gigascience/giz022 · Cited by 61 · see citing works
A k-mer grammar analysis to uncover maize regulatory architecture
Mejía-Guerra, M. K., & Buckler, E. (2019) · BMC Plant Biology · doi:10.1186/s12870-019-1693-2 · Cited by 58 · see citing works
Detecting natural selection on cis-regulatory DNA
Hahn, M. W. (2006) · Genetica · doi:10.1007/s10709-006-0029-y · Cited by 55 · see citing works
An improved short‐lived fluorescent protein transcriptional reporter for Saccharomyces cerevisiae
Houser, J. R., Ford, E., Chatterjea, S. M., Maleri, S., Elston, T. C., & Errede, B. (2012) · Yeast · doi:10.1002/yea.2932 · Cited by 53 · see citing works
Species-specific factors mediate extensive heterogeneity of mRNA 3′ ends in yeasts
Moqtaderi, Z., Geisberg, J. V., Jin, Y., Fan, X., & Struhl, K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309384110 · Cited by 50 · see citing works
Pol II promoter prediction using characteristic 4-mer motifs: a machine learning approach
Anwar, F., Baker, S. M., Jabid, T., Hasan, M. M., Shoyaib, M., Khan, H., & Walshe, R. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-414 · Cited by 50 · see citing works
Enhancer–gene maps in the human and zebrafish genomes using evolutionary linkage conservation
Clément, Y., Torbey, P., Gilardi‐Hebenstreit, P., & Crollius, H. R. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1199 · Cited by 41 · see citing works
Chi-squared computation for association rules: preliminary results
Álvarez, S. A. (2003) · Cited by 39 · see citing works
Building synthetic gene circuits from combinatorial libraries: screening and selection strategies
Schaerli, Y., & Isalan, M. (2013) · Molecular BioSystems · doi:10.1039/c2mb25483b · Cited by 37 · see citing works
Fay, J. C., & Benavides, J. A. (2005) · Genetics · doi:10.1534/genetics.105.042283 · Cited by 34 · see citing works
Correlating Gene Expression Variation with cis-Regulatory Polymorphism in Saccharomyces cerevisiae
Chen, K. M., van Nimwegen, E., Rajewsky, N., & Siegal, M. L. (2010) · Genome Biology and Evolution · doi:10.1093/gbe/evq054 · Cited by 29 · see citing works
Morse, N. J., Gopal, M. R., Wagner, J. M., & Alper, H. S. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.7b00138 · Cited by 28 · see citing works
Cuperus, J. T., Groves, B., Kuchina, A., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/137547 · Cited by 26 · see citing works
Towards better understanding of gradient-based attribution methods for Deep Neural NetworksPreprint
Ancona, M., Ceolini, E., Öztireli, C., et al. (2017) · Zurich Open Repository and Archive (University of Zurich) · doi:10.48550/arxiv.1711.06104 · Cited by 26 · see citing works
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Cohn, D., Zuk, O., & Kaplan, T. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/264200 · Cited by 25 · see citing works
Holland, P., Bergenholm, D., Börlin, C. S., Liu, G., & Nielsen, J. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz253 · Cited by 25 · see citing works
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Espinar, L., Schikora-Tamarit, M. À., Domingo, J., & Carey, L. B. (2018) · Genome Research · doi:10.1101/gr.230458.117 · Cited by 21 · see citing works
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Koo, P. K., & Eddy, S. R. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/362756 · Cited by 20 · see citing works
A genomic study of the inter‐ORF distances in Saccharomyces cerevisiae
Pelechano, V., García‐Martínez, J., & Pérez-Ortín, J. E. (2006) · Yeast · doi:10.1002/yea.1390 · Cited by 16 · see citing works
Probing instructions for expression regulation in gene nucleotide compositions
Bessière, C., Taha, M., Petitprez, F., Vandel, J., Marin, J., Bréhélin, L., Lèbre, S., & Lecellier, C. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005921 · Cited by 15 · see citing works
Performance of Regression Models as a Function of Experiment Noise
Li, G., Zrimec, J., Ji, B., Geng, J., Larsbrink, J., Zelezniak, A., Nielsen, J., & Engqvist, M. K. M. (2021) · Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) · Cited by 14 · see citing works
Self-citationImpact of retrofitted CPU water cooling on supercomputer performance and power consumption
Ovaska, S. J., Dragseth, R. E., & Hanssen, S. A. (2016) · Proceedings of IEEE Southeastcon · doi:10.1109/secon.2016.7506669 · Cited by 13 · see citing works
Correction: Evolutionary principles of modular gene regulation in yeasts
Thompson, D. A., Roy, S., Chan, M. M., Styczynski, M. P., Pfiffner, J., French, C. E., Socha, A. L., Thielke, A. L., Napolitano, S., Muller, P. A., et al. (2013) · eLife · doi:10.7554/elife.01114 · Cited by 12 · see citing works
Patterns of variation in cis-regulatory regions: examining evidence of purifying selection
Naidoo, T., Sjödin, P., Schlebusch, C. M., & Jakobsson, M. (2018) · BMC Genomics · doi:10.1186/s12864-017-4422-y · Cited by 12 · see citing works
Zhang, P., Du, G., Zou, H., Xie, G., Chen, J., Shi, Z., & Zhou, J. (2016) · Scientific Reports · doi:10.1038/srep33970 · Cited by 10 · see citing works
Rabani, M., Pieper, L. M., Chew, G.-L., & Schier, A. F. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.04.013 · Cited by 10 · see citing works
Fast Prediction of DNA Melting Bubbles Using DNA Thermodynamic Stability
Zrimec, J., & Lapanje, A. (2015) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2015.2396057 · Cited by 8 · see citing works
Self-citationA bioinformatic pipeline to analyze ChIP-exo datasets
Börlin, C. S., Bergenholm, D., Holland, P., & Nielsen, J. (2019) · Biology Methods and Protocols · doi:10.1093/biomethods/bpz011 · Cited by 4 · see citing works
Self-citationZrimec, J. (2020) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.4071761 · Cited by 1 · see citing works
Self-citationZrimec, J. (2020) · Zenodo · doi:10.5281/zenodo.4071762
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [82]Kuhn, M. & Johnson, K. Applied predictive modelling. (Springer, New York, Heidelberg, Dordrecht, London, 2013).
- [85]Shalizi, C. Advanced data analysis from an elementary point of view. (Cambridge University Press, 2013).
Cited by
Sorted by citations
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Li, F., Yuan, L., Lu, H., Li, G., Chen, Y., Engqvist, M. K. M., Kerkhoven, E. J., & Nielsen, J. (2022) · Nature Catalysis · doi:10.1038/s41929-022-00798-z · Cited by 466 · see citing works
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Adlung, L., Cohen, Y., Mor, U., & Elinav, E. (2021) · Med · doi:10.1016/j.medj.2021.04.006 · Cited by 304 · see citing works
Kim, J. I., Maguire, F., Tsang, K. K., Gouliouris, T., Peacock, S. J., McAllister, T. A., McArthur, A. G., & Beiko, R. G. (2022) · Clinical Microbiology Reviews · doi:10.1128/cmr.00179-21 · Cited by 278 · see citing works
Goshisht, M. K. (2024) · ACS Omega · doi:10.1021/acsomega.3c05913 · Cited by 169 · see citing works
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Alharbi, W., & Rashid, M. (2022) · Human Genomics · doi:10.1186/s40246-022-00396-x · Cited by 161 · see citing works
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Guo, Z., Liu, J., Wang, Y., Chen, M., Wang, D., Xu, D., & Cheng, J. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00114-9 · Cited by 163 · see citing works
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Mendoza‐Revilla, J., Trop, E., Gonzalez, L., Roller, M., Dalla-Torre, H., de Almeida, B. P., Richard, G., Caton, J., Carranza, N. L., Skwark, M. J., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06465-2 · Cited by 122 · see citing works
Yasmeen, E., Wang, J., Riaz, M., Zhang, L., & Zuo, K. (2023) · Plant Communications · doi:10.1016/j.xplc.2023.100558 · Cited by 106 · see citing works
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Self-citationPredicting gene expression from DNA sequence using deep learning models
Barbadilla-Martínez, L., Klaassen, N. H. M., van Steensel, B., & de Ridder, J. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00841-2 · Cited by 83 · see citing works
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Smet, D., Opdebeeck, H., & Vandepoele, K. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2023.1212073 · Cited by 28 · see citing works
Gardiner, L., Rusholme‐Pilcher, R., Colmer, J., Rees, H., Crescente, J. M., Carrieri, A. P., Duncan, S. H., Pyzer‐Knapp, E. O., Krishna, R., & Hall, A. J. W. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2103070118 · Cited by 28 · see citing works
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Milito, A., Aschern, M., McQuillan, J. L., & Yang, J. (2023) · Journal of Experimental Botany · doi:10.1093/jxb/erad100 · Cited by 25 · see citing works
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Cui, Y., Zhang, Z., Shi, Y., & Hu, Y. (2025) · Journal of Materials Chemistry B · doi:10.1039/d4tb02876g · Cited by 22 · see citing works
Barazandeh, S., Özden, F., Hınçer, A., Şeker, U. Ö. Ş., & Çiçek, A. E. (2024) · Bioinformatics Advances · doi:10.1093/bioadv/vbaf134 · Cited by 23 · see citing works
Transcriptional regulation in plants: Using omics data to crack the cis-regulatory code
Zemlyanskaya, E. V., Dolgikh, V. A., Levitsky, V. G., & Mironova, V. (2021) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2021.102058 · Cited by 22 · see citing works
Precise engineering of gene expression by editing plasticity
Qiu, Y., Liu, L., Yan, J., Xianglei, X., Wang, S., Luo, Y., Deng, K., Xu, J., Jin, M., Wu, X., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03516-7 · Cited by 21 · see citing works
Unveiling the frontiers of deep learning: Innovations shaping diverse domains
Ahmed, S. F., Alam, M. S. B., Kabir, M., Afrin, S., Rafa, S. J., Mehjabin, A., & Gandomi, A. H. (2025) · Applied Intelligence · doi:10.1007/s10489-025-06259-x · Cited by 26 · see citing works
Wang, Z., Peng, Y., Li, J., Li, J., Yuan, H., Yang, S., Ding, X., Xie, A., Zhang, J., Wang, S., et al. (2024) · Plant Communications · doi:10.1016/j.xplc.2024.100985 · Cited by 20 · see citing works
Programmed versus non-programmed evolution of aging. What is the evidence?
Pamplona, R., Jové, M., Gómez, J., & Barja, G. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112162 · Cited by 20 · see citing works
Constant, D. A., Gutierrez, J. M., Sastry, A. V., Viazzo, R., Smith, N. R., Hossain, J., Spencer, D. A., Carter, H., Ventura, A. B., Louie, M. T. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.11.528149 · Cited by 20 · see citing works
Levy, B., Xu, Z., Zhao, L., Kremling, K. A. G., Altman, R., Wong, P., & Tanner, C. (2022) · Research Square · doi:10.21203/rs.3.rs-1927200/v1 · Cited by 19 · see citing works
From text to traits: exploring the role of large language models in plant breeding
Yoosefzadeh-Najafabadi, M. (2025) · Frontiers in Plant Science · doi:10.3389/fpls.2025.1583344 · Cited by 19 · see citing works
Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications
Clauer, P. R., Nou, A., Toth, T., Yu, Q., Chemla, Y., Boo, A., Yoon, K. S., & Voigt, C. A. (2026) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00687 · Cited by 20 · see citing works
Ma, X., Ma, L., & Huo, Y. (2021) · Trends in biotechnology · doi:10.1016/j.tibtech.2021.11.002 · Cited by 17 · see citing works
A multi-scale transcriptional regulatory network knowledge base for Escherichia coliPreprint
Lamoureux, C. R., Decker, K., Sastry, A. V., Rychel, K., Gao, Y., McConn, J. L., Zielinski, D. C., & Palsson, B. Ø. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.08.439047 · Cited by 17 · see citing works
Markova, E. A., Shaw, R. E., & Reynolds, C. R. (2022) · Engineering Biology · doi:10.1049/enb2.12025 · Cited by 16 · see citing works
mRNA-LM: full-length integrated SLM for mRNA analysis
Li, S., Noroozizadeh, S., Moayedpour, S., Kogler-Anele, L., Xue, Z., Zheng, D., Montoya, F. U., Agarwal, V., Bar‐Joseph, Z., & Jäger, S. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf044 · Cited by 17 · see citing works
High-Dimensional Single-Cell Transcriptomics in Melanoma and Cancer Immunotherapy
Quek, C. Y. J., Bai, X., Long, G. V., Scolyer, R. A., & Wilmott, J. S. (2021) · Genes · doi:10.3390/genes12101629 · Cited by 16 · see citing works
De novo promoter design method based on deep generative and dynamic evolution algorithm
Gu, Y., Su, J., Xia, J., Wu, P., Wu, H., Su, Y., Wei, P.-J., & Zheng, C.-H. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf833 · Cited by 14 · see citing works
The Expanding Computational Toolbox for Engineering Microbial Phenotypes at the Genome Scale
Zielinski, D. C., Patel, A., & Palsson, B. Ø. (2020) · Microorganisms · doi:10.3390/microorganisms8122050 · Cited by 14 · see citing works
Performance of Regression Models as a Function of Experiment Noise
Li, G., Zrimec, J., Ji, B., Geng, J., Larsbrink, J., Zelezniak, A., Nielsen, J., & Engqvist, M. K. M. (2021) · Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) · Cited by 14 · see citing works
Self-citationFrontiers and techniques in plant gene regulation
Jores, T., Hamm, M. O., Cuperus, J. T., & Queitsch, C. (2023) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2023.102403 · Cited by 14 · see citing works
Orantes-Bonilla, M., Wang, H., Lee, H., Golicz, A. A., Hu, D., Li, W., Zou, J., & Snowdon, R. J. (2023) · Theoretical and Applied Genetics · doi:10.1007/s00122-023-04345-7 · Cited by 13 · see citing works
Popović, M. C., Stanišić, M. D., & Prodanović, R. (2024) · Fermentation · doi:10.3390/fermentation10020093 · Cited by 13 · see citing works
Lin, J., Luo, R., & Pinello, L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.01.606099 · Cited by 13 · see citing works
Predicting gene expression state and prioritizing putative enhancers using 5hmC signal
González‐Avalos, E., Onodera, A., Samaniego‐Castruita, D., Rao, A., & Ay, F. (2024) · Genome biology · doi:10.1186/s13059-024-03273-z · Cited by 12 · see citing works
Rich, A., Acar, O., & Carvunis, A. (2024) · Genome biology · doi:10.1186/s13059-024-03287-7 · Cited by 11 · see citing works
Amino acid sequence encodes protein abundance shaped by protein stability at reduced synthesis cost
(2024) · doi:10.1002/pro.5239 · Cited by 12 · see citing works
Self-citationChromatin enables precise and scalable gene regulation with factors of limited specificity
Perkins, M. L., Crocker, J., & Tkačik, G. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2411887121 · Cited by 11 · see citing works
Intelligent host engineering for metabolic flux optimisation in biotechnology
Munro, L. J., & Kell, D. B. (2021) · Biochemical Journal · doi:10.1042/bcj20210535 · Cited by 12 · see citing works
Inference on the structure of gene regulatory networks
Wang, Y., & Wang, Z. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2022.111055 · Cited by 13 · see citing works
Multigene engineering in plants: Technologies, applications, and future prospects
Rajput, R., Boone, B. A., Mandlik, R., Islam, M. T., Qi, Y., Wang, J., Barrangou, R., Sozzani, R., Eckert, C. A., Tuskan, G. A., et al. (2025) · Biotechnology Advances · doi:10.1016/j.biotechadv.2025.108697 · Cited by 11 · see citing works
Advances in promoter engineering strategies for enhanced recombinant protein expression in plants
Sadravi, S., Lee, J., & JianFeng, X. (2026) · Frontiers in Plant Science · doi:10.3389/fpls.2025.1747353 · Cited by 11 · see citing works
DeePromClass: Delineator for Eukaryotic Core Promoters Employing Deep Neural Networks
Kari, H., Bandi, S. M. S., Kumar, A., & Yella, V. R. (2022) · IEEE/ACM Transactions on Computational Biology & Bioinformatics · doi:10.1109/tcbb.2022.3163418 · Cited by 8 · see citing works
Interpretable deep residual network uncovers nucleosome positioning and associated features
Masoudi‐Sobhanzadeh, Y., Li, S., Peng, Y., & Panchenko, A. R. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae623 · Cited by 11 · see citing works
Chen, H., Yang, Y., & Dong, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-87663-8 · Cited by 11 · see citing works
FUN-PROSE: A deep learning approach to predict condition-specific gene expression in fungi
Nambiar, A., Dubinkina, V. B., Liu, S., & Maslov, S. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011563 · Cited by 10 · see citing works
Prinz, R., Bücher, P., Kun, Á., Paredes, O., Aragno, A., Shelby, C. L., Gumbel, M., Fimmel, E., & Strüngmann, L. (2025) · Biosystems · doi:10.1016/j.biosystems.2025.105515 · Cited by 9 · see citing works
In silico prediction of variant effects: promises and limitations for precision plant breeding
Sendrowski, J., Bataillon, T. M., & Ramstein, G. P. (2025) · Theoretical and Applied Genetics · doi:10.1007/s00122-025-04973-1 · Cited by 10 · see citing works
A Genetic Algorithm-Based Ensemble Learning Framework for Drug Combination Prediction
Wu, L., Ye, X., Zhang, Y., Gao, J., Lin, Z., Sui, B., Wen, Y., Wu, Q., Liu, K., He, S., et al. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00260 · Cited by 10 · see citing works
Szymczyk, P., & Majewska, M. (2024) · Applied Sciences · doi:10.3390/app14114877 · Cited by 10 · see citing works
Cutting-edge deep-learning based tools for metagenomic research
Karin, E. L., & Steinegger, M. (2025) · National Science Review · doi:10.1093/nsr/nwaf056 · Cited by 10 · see citing works
Generation of Realistic Gene Regulatory Networks by Enriching for Feed-Forward Loops
Zhivkoplias, E. K., Vavulov, O., Hillerton, T., & Sonnhammer, E. L. L. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.815692 · Cited by 8 · see citing works
Gao, S., Rehman, J., & Dai, Y. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.07.014 · Cited by 7 · see citing works
Feasibility of predicting allele specific expression from DNA sequencing using machine learning
Zhang, Z., van Dijk, F., de Klein, N., van Gijn, M. E., Franke, L., Sinke, R. J., Swertz, M. A., & van der Velde, K. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-89904-y · Cited by 9 · see citing works
Toward learning the principles of plant gene regulation
Zrimec, J., Zelezniak, A., & Gruden, K. (2022) · Trends in Plant Science · doi:10.1016/j.tplants.2022.08.010 · Cited by 8 · see citing works
Self-citationMachine learning applications for transcription level and phenotype predictions
Chantaraamporn, J., Phumikhet, P., Nguantad, S., Techo, T., & Charoensawan, V. (2022) · IUBMB Life · doi:10.1002/iub.2693 · Cited by 8 · see citing works
Deep Learning for Lung Cancer Nodal Staging and Real-World Clinical Practice
Park, C. M., & Lee, J. H. (2021) · Radiology · doi:10.1148/radiol.2021211981 · Cited by 8 · see citing works
Predicting cold-stress responsive genes in cotton with machine learning models
Zhang, M., Deng, Y., Shi, W., Wang, L., Zhou, N., Wang, H., Zhang, Z., Guan, X., & Zhao, T. (2024) · Crop Design · doi:10.1016/j.cropd.2024.100085 · Cited by 7 · see citing works
Rashid, A., Al-Obeidat, F. N., Hafez, W., Benakatti, G., Malik, R. A., Koutentis, C. A., Sharief, J., Brierley, J., Quraishi, N. A., Malik, Z. A., et al. (2023) · Shock · doi:10.1097/shk.0000000000002227 · Cited by 7 · see citing works
Shrimankar, D. D., Durge, A. R., & Sawarkar, A. D. (2022) · Current Genomics · doi:10.2174/1389202923666220927105311 · Cited by 7 · see citing works
Sequence-based modelling of bacterial genomes enables accurate antibiotic resistance predictionPreprint
Wiatrak, M., Weimann, A., Dinan, A. M., Brbić, M., & Floto, R. A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.03.574022 · Cited by 7 · see citing works
Toward Identification of Functional Sequences and Variants in Noncoding DNA
Monti, R., & Ohler, U. (2023) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-122120-110102 · Cited by 6 · see citing works
Wang, C. C. Q., Dong, Y., Li, C., Oberstaller, J., Zhang, M., Gibbons, J., Pires, C. V., Xiao, M., Zhu, L., Jiang, R. H. Y., et al. (2023) · Genome biology · doi:10.1186/s13059-023-03063-z · Cited by 6 · see citing works
Zeng, J., Song, K., Wang, J., Wen, H., Zhou, J., Ni, T., Lü, H., & Yu, Y. (2024) · Microbial Cell Factories · doi:10.1186/s12934-023-02271-3 · Cited by 6 · see citing works
- Authors
- Zrimec, J., Börlin, C. S., Buric, F., Muhammad, A. S., Chen, R., Siewers, V., Verendel, V., Nielsen, J., Töpel, M., & Zelezniak, A.
- Affiliations
- Chalmers University of Technology (SE)
- University of Gothenburg (SE)
- Science for Life Laboratory (SE)
- Corresponding author
- Zelezniak, Aleksej
- ORCID
- Venue
- Nature Communications
- Published
- 2020-12-01
- Volume
- 11
- Issue
- 1
- Pages
- 6141-6141
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7708451
- OpenAlex
- W3108101741
- Cited by
- 174
- References
- 154
- Citations by year
- 2026: 19 · 2025: 35 · 2024: 42 · 2023: 28 · 2022: 27 · 2021: 21 · 2020: 2
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Nvidia
- European Commission (722287)
- Chalmers Tekniska Högskola
- Science for Life Laboratory
- Novo Nordisk Fonden (NNF10CC1016517)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- gene expression regulation, mRNA levels, DNA sequences, regulatory motifs, coevolution, non-coding regions, coding sequences, deep learning, transcriptome, model organisms
- MeSH terms
- Deep Learning, Animals, Bacteria, Base Sequence, Drosophila melanogaster, Gene Expression Regulation, Humans, Regulatory Sequences, Nucleic Acid, RNA, Messenger, Saccharomyces cerevisiae, Evolution, Molecular, Mice
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