Laboratory of Functional and Structural Genomics

Profile

Prof. Dariusz Plewczyński
e-mail: d.plewczynski@cent.uw.edu.pl
phone: +48 22 55 43654
room: 03.63
ORCID: 0000-0002-3840-7610
SCOPUS ID: 6602719966

In the Laboratory of Functional and Structural Genomics we perform theoretical studies, whose main objective is to analyze and predict the three-dimensional structure of the human genome, and its relation with the genomic diversity of human populations, both natural and pathological. In particular, we investigate structural variants, copy number variants observed in various sub-populations and the groups of patients, and their three-dimensional localization in the structure of the nucleus.

We also examine the relationship of the expression levels of selected genes from their location in three-dimensional space. In addition, we use structural information to enrich the sequential genomic analysis in order to better define the function of selected genomic regions that are important in the context of personalized medicine.

For this purpose, first we are developing a variety of large-scale computational tools for analysis of whole genome sequences, the identification of structural variants, determining the statistical significance of the observed number of copies of genomic regions in selected cohorts of patients. Secondly, we evaluate their uniqueness comparing the observed changes with typical and natural genomic diversity that has been cataloged for example in the 1000 Genomes Project Consortium. Thirdly, we infer the biological function of these genomic regions using publicly available databases. Fourthly, we identify unique local three-dimensional environment for selected sites, eg. regulatory ones. In the fifth step, we analyze the impact of structural re-arrangements of those local neighborhoods on the gene expression profiles, which is related to the presence of transcription factories.

Dariusz Plewczynski interests are focused on functional and structural genomics. Functional genomic attempts to make use of the vast wealth of data produced by high- throughput genomics projects, such as the structural genomics consortia, Human genome project, 1000 Genomes Project, ENCODE, and many others. The major tools that are used in this interdisciplinary research endeavor include statistical data analysis (GWAS studies, clustering, machine learning), genomic variation analysis using diverse data sources (karyotyping, confocal microscopy, aCGH microarrays, next generation sequencing: both whole genome and whole exome), bioinformatics (protein sequence analysis, protein structure prediction), and finally biophysics (polymer theory and simulations) and genomics (epigenetics, genome domains, three dimensional structure analysis of chromatin). He is presently involved in several Big Data projects at three institutes: Centre of New Technologies at University of Warsaw (his main affiliation), Jackson Laboratory for Genomic Medicine (an international partner of the TEAM project), and The Centre for Innovative Research (within the Leading National Research Centre KNOW 2012-2017) at Medical University of Bialystok (UMB). He is participating in two large projects, namely 1000 Genomes Project (NIH) by bioinformatics analysis of genomic data from aCGH arrays and NGS (next generation sequencing, deep coverage) experiments for structural variants (SV) identification; and biophysical modeling of chromatin three-dimensional conformation inside human cells using HiC and ChIA-PET techniques within the 4D Nucleome project funded by the NIH in the USA. His goal is to combine the SV data with three-dimensional cell nucleus structure for better understanding of normal genomic variation among human populations, the natural selection process during the human evolution, mammalian cell differentiation, and finally the origin, pathways, progression and development of cancer and autoimmune diseases.

Team

Leader
Prof. Dariusz Plewczyński

Postdocs
Joanna Borkowska, PhD
Anup Kumar Halder, PhD
Karolina Jodkowska, PhD

PhD Students
Abhishek Agarwal, MSc
Krzysztof Banecki, MSc
Mateusz Chiliński, MSc, Eng
Sachin Gadakh, MSc
Sebastian Korsak, MSc
Zofia Tojek, MSc
Maciej Wiśniewski, MSc

Students
Jakub Józefowicz
Jędrzej Kubica
Joanna Młodziejewska
inż. Marek Sokołowski

Selected projects

Selected publications

• Korsak S., Banecki K., Plewczynski D.
  Multiscale molecular modeling of chromatin with MultiMM: From nucleosomes to the whole genome
  (2024) Computational and Structural Biotechnology Journal, 23, pp. 3537 – 3548
  DOI: 10.1016/j.csbj.2024.09.025
• Kumar Halder A., Agarwal A., Jodkowska K., Plewczynski D.
  A systematic analyses of different bioinformatics pipelines for genomic data and its impact on deep learning models for chromatin loop prediction
  (2024) Briefings in Functional Genomics, 23 (5), pp. 538 – 548
  DOI: 10.1093/bfgp/elae009
• Fichna J.P., Chiliński M., Halder A.K., Cięszczyk P., Plewczynski D., Żekanowski C., Janik P.
  Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome
  (2024) International Journal of Molecular Sciences, 25 (11), art. no. 5758
  DOI: 10.3390/ijms25115758
• Banecki K., Korsak S., Plewczynski D.
  Advancements and future directions in single-cell Hi-C based 3D chromatin modeling
  (2024) Computational and Structural Biotechnology Journal, 23, pp. 3549 – 3558
  DOI: 10.1016/j.csbj.2024.09.026
• Chiliński M., Plewczynski D.
  HiCDiffusion – diffusion-enhanced, transformer-based prediction of chromatin interactions from DNA sequences
  (2024) BMC Genomics, 25 (1), art. no. 964
  DOI: 10.1186/s12864-024-10885-z
• Kadlof M., Banecki K., Chiliński M., Plewczynski D.
  Chromatin image-driven modelling
  (2024) Methods, 226, pp. 54 – 60
  DOI: 10.1016/j.ymeth.2024.04.006
• Kokot A., Gadakh S., Saha I., Gajda E., Łaźniewski M., Rakshit S., Sengupta K., Mollah A.F., Denkiewicz M., Górczak K., Claesen J., Burzykowski T., Plewczynski D.
  Unveiling the Molecular Mechanism of Trastuzumab Resistance in SKBR3 and BT474 Cell Lines for HER2 Positive Breast Cancer
  (2024) Current Issues in Molecular Biology, 46 (3), pp. 2713 – 2740
  DOI: 10.3390/cimb46030171
• Chiliński M., Lipiński J., Agarwal A., Ruan Y., Plewczynski D.
  Enhanced performance of gene expression predictive models with protein-mediated spatial chromatin interactions
  (2023) Scientific Reports, 13 (1), art. no. 11693
  DOI: 10.1038/s41598-023-38865-5
• Korsak S., Plewczynski D.
  LoopSage: An energy-based Monte Carlo approach for the loop extrusion modeling of chromatin
  (2024) Methods, 223, pp. 106 – 117
  DOI: 10.1016/j.ymeth.2024.01.015
• Ghosh N., Saha I., Plewczynski D.
  Editorial: Unveiling novel aspects of SARS-CoV-2 to combat COVID-19
  (2024) Frontiers in Genetics, 15, art. no. 1383640
  DOI: 10.3389/fgene.2024.1383640

Contact

Prof. Dariusz Plewczyński
e-mail: d.plewczynski@cent.uw.edu.pl
phone: +48 22 55 43654
room: 03.63