Basal cell carcinoma (BCC) of the skin is the most common cancer in humans, characterized by the ... more Basal cell carcinoma (BCC) of the skin is the most common cancer in humans, characterized by the highest mutation rate among cancers, and is mostly driven by mutations in genes involved in the hedgehog pathway. To date, almost all BCC genetic studies have focused exclusively on protein-coding sequences; therefore, the impact of noncoding variants on the BCC genome is unrecognized. In this study, with the use of whole-exome sequencing of 27 tumor/normal pairs of BCC samples, we performed an analysis of somatic mutations in both protein-coding sequences and gene-associated noncoding regions, including 5’UTRs, 3’UTRs, and exon-adjacent intron sequences. Separately, in each region, we performed hotspot identification, mutation enrichment analysis, and cancer driver identification with OncodriveFML. Additionally, we performed a whole-genome copy number alteration analysis with GISTIC2. Of the >80,000 identified mutations, ~50% were localized in noncoding regions. The results of the an...
Background: Breast cancer affects over 2 million women yearly. Its early detection allows for suc... more Background: Breast cancer affects over 2 million women yearly. Its early detection allows for successful treatment, which motivates to research factors that enable an accurate diagnosis. miR-125a is one of them, correlating with different types of cancer. For example, the miR-125a level decreases in breast cancer tissues; polymorphisms in the miR-125a encoding gene are related to prostate cancer and the risk of radiotherapy-induced pneumonitis. Methods: In this work, we investigated two variants of rs12976445 polymorphism in the context of breast cancer. We analyzed the data of 175 blood samples from breast cancer patients and compared them with the control data from 129 control samples. Results: We observed the tendency that in breast cancer cases TT genotype appeared slightly more frequent over CC and CT genotypes (statistically nonsignificant). The TT genotype appeared also to be more frequent among human epidermal growth factor receptor 2 (HER2) positive patients, compared to HE...
The catalytic effects of complex minerals or meteorites are often mentioned as important factors ... more The catalytic effects of complex minerals or meteorites are often mentioned as important factors for the origins of life. To assess the possible role of nanoconfinement within a catalyst consisting of montmorillonite (MMT) and the impact of local electric field on the formation efficiency of the simple hypothetical precursors of nucleic acid bases or amino acids, we performed ab initio Car–Parrinello molecular dynamics simulations. We prepared four condensed-phase systems corresponding to previously suggested prototypes of a primordial soup. We monitored possible chemical reactions occurring within gas-like bulk and MMT-confined four simulation boxes on a 20-ps time scale at 1 atm and 300 K, 400 K, and 600 K. Elevated temperatures did not affect the reactivity of the elementary components of the gas-like boxes considerably; however, the presence of the MMT nanoclay substantially increased the formation probability of new molecules. Approximately 20 different new compounds were found...
Background: Open science is an emerging movement underlining the importance of transparent, high ... more Background: Open science is an emerging movement underlining the importance of transparent, high quality research where results can be verified and reused by others. However, one of the biggest problems in replicating experiments is the lack of access to the data used by the authors. This problem also occurs during mathematical modeling of a viral infections. It is a process that can provide valuable insights into viral activity or into a drug’s mechanism of action when conducted correctly. Objective: We present the VirDB database (virdb.cs.put.poznan.pl), which has two primary objectives. First, it is a tool that enables collecting data on viral infections that could be used to develop new dynamic models of infections using the FAIR data sharing principles. Second, it allows storing references to descriptions of viral infection models, together with their evaluation results. Methods: To facilitate the fast population of database and the ease of exchange of scientific data, we decid...
According to some hypotheses, from a statistical perspective the origin of life seems to be a hig... more According to some hypotheses, from a statistical perspective the origin of life seems to be a highly improbable event. Although there is no rigid definition of life itself, life as it is, is a fact. One of the most recognized hypotheses for the origins of life is the RNA world hypothesis. Laboratory experiments have been conducted to prove some assumptions of the RNA world hypothesis. However, despite some success in the ‘wet-lab’, we are still far from a complete explanation. Bioinformatics, supported by biomathematics, appears to provide the perfect tools to model and test various scenarios of the origins of life where wet-lab experiments cannot reflect the true complexity of the problem. Bioinformatics simulations of early pre-living systems may give us clues to the mechanisms of evolution. Whether or not this approach succeeds is still an open question. However, it seems likely that linking efforts and knowledge from the various fields of science into a holistic bioinformatics p...
A hypercycle is an abstract model of organization of self-replicating molecules connected in a cy... more A hypercycle is an abstract model of organization of self-replicating molecules connected in a cyclic, autocatalytic manner. It was introduced in an ordinary differential equation (ODE) form by the Nobel Prize winner Manfred Eigen in 1971 [1] and subsequently further extended in collaboration with Peter Schuster [2,3]. It was proposed as a solution to the error threshold problem encountered during modelling of replicative molecules that hypothetically existed on the primordial Earth (see: abiogenesis). The hypercycle is a special case of the replicator equation [4]. The most important properties of hypercycles are autocatalytic growth competition between cycles, once-for-ever selective behaviour, utilization of small selective advantage, rapid evolvability, increased information capacity, and selection against parasitic branches.
The function of RNA is strongly dependent on its structure, so an appropriate recognition of this... more The function of RNA is strongly dependent on its structure, so an appropriate recognition of this structure, on every level of organization, is of great importance. One particular concern is the assessment of base-base interactions, described as the secondary structure, the knowledge of which greatly facilitates an interpretation of RNA function and allows for structure analysis on the tertiary level. The RNA secondary structure can be predicted from a sequence using in silico methods often adjusted with experimental data, or assessed from 3D structure atom coordinates. Computational approaches typically consider only canonical, Watson-Crick and wobble base pairs. Handling of non-canonical interactions, important for a full description of RNA structure, is still very difficult. We introduce our novel approach to assessing an extended RNA secondary structure, which characterizes both canonical and non-canonical base pairs, along with their type classification. It is based on predicti...
Basal cell carcinoma (BCC) of the skin is the most common cancer in humans, characterized by the ... more Basal cell carcinoma (BCC) of the skin is the most common cancer in humans, characterized by the highest mutation rate among cancers, and is mostly driven by mutations in genes involved in the hedgehog pathway. To date, almost all BCC genetic studies have focused exclusively on protein-coding sequences; therefore, the impact of noncoding variants on the BCC genome is unrecognized. In this study, with the use of whole-exome sequencing of 27 tumor/normal pairs of BCC samples, we performed an analysis of somatic mutations in both protein-coding sequences and gene-associated noncoding regions, including 5’UTRs, 3’UTRs, and exon-adjacent intron sequences. Separately, in each region, we performed hotspot identification, mutation enrichment analysis, and cancer driver identification with OncodriveFML. Additionally, we performed a whole-genome copy number alteration analysis with GISTIC2. Of the >80,000 identified mutations, ~50% were localized in noncoding regions. The results of the an...
Background: Breast cancer affects over 2 million women yearly. Its early detection allows for suc... more Background: Breast cancer affects over 2 million women yearly. Its early detection allows for successful treatment, which motivates to research factors that enable an accurate diagnosis. miR-125a is one of them, correlating with different types of cancer. For example, the miR-125a level decreases in breast cancer tissues; polymorphisms in the miR-125a encoding gene are related to prostate cancer and the risk of radiotherapy-induced pneumonitis. Methods: In this work, we investigated two variants of rs12976445 polymorphism in the context of breast cancer. We analyzed the data of 175 blood samples from breast cancer patients and compared them with the control data from 129 control samples. Results: We observed the tendency that in breast cancer cases TT genotype appeared slightly more frequent over CC and CT genotypes (statistically nonsignificant). The TT genotype appeared also to be more frequent among human epidermal growth factor receptor 2 (HER2) positive patients, compared to HE...
The catalytic effects of complex minerals or meteorites are often mentioned as important factors ... more The catalytic effects of complex minerals or meteorites are often mentioned as important factors for the origins of life. To assess the possible role of nanoconfinement within a catalyst consisting of montmorillonite (MMT) and the impact of local electric field on the formation efficiency of the simple hypothetical precursors of nucleic acid bases or amino acids, we performed ab initio Car–Parrinello molecular dynamics simulations. We prepared four condensed-phase systems corresponding to previously suggested prototypes of a primordial soup. We monitored possible chemical reactions occurring within gas-like bulk and MMT-confined four simulation boxes on a 20-ps time scale at 1 atm and 300 K, 400 K, and 600 K. Elevated temperatures did not affect the reactivity of the elementary components of the gas-like boxes considerably; however, the presence of the MMT nanoclay substantially increased the formation probability of new molecules. Approximately 20 different new compounds were found...
Background: Open science is an emerging movement underlining the importance of transparent, high ... more Background: Open science is an emerging movement underlining the importance of transparent, high quality research where results can be verified and reused by others. However, one of the biggest problems in replicating experiments is the lack of access to the data used by the authors. This problem also occurs during mathematical modeling of a viral infections. It is a process that can provide valuable insights into viral activity or into a drug’s mechanism of action when conducted correctly. Objective: We present the VirDB database (virdb.cs.put.poznan.pl), which has two primary objectives. First, it is a tool that enables collecting data on viral infections that could be used to develop new dynamic models of infections using the FAIR data sharing principles. Second, it allows storing references to descriptions of viral infection models, together with their evaluation results. Methods: To facilitate the fast population of database and the ease of exchange of scientific data, we decid...
According to some hypotheses, from a statistical perspective the origin of life seems to be a hig... more According to some hypotheses, from a statistical perspective the origin of life seems to be a highly improbable event. Although there is no rigid definition of life itself, life as it is, is a fact. One of the most recognized hypotheses for the origins of life is the RNA world hypothesis. Laboratory experiments have been conducted to prove some assumptions of the RNA world hypothesis. However, despite some success in the ‘wet-lab’, we are still far from a complete explanation. Bioinformatics, supported by biomathematics, appears to provide the perfect tools to model and test various scenarios of the origins of life where wet-lab experiments cannot reflect the true complexity of the problem. Bioinformatics simulations of early pre-living systems may give us clues to the mechanisms of evolution. Whether or not this approach succeeds is still an open question. However, it seems likely that linking efforts and knowledge from the various fields of science into a holistic bioinformatics p...
A hypercycle is an abstract model of organization of self-replicating molecules connected in a cy... more A hypercycle is an abstract model of organization of self-replicating molecules connected in a cyclic, autocatalytic manner. It was introduced in an ordinary differential equation (ODE) form by the Nobel Prize winner Manfred Eigen in 1971 [1] and subsequently further extended in collaboration with Peter Schuster [2,3]. It was proposed as a solution to the error threshold problem encountered during modelling of replicative molecules that hypothetically existed on the primordial Earth (see: abiogenesis). The hypercycle is a special case of the replicator equation [4]. The most important properties of hypercycles are autocatalytic growth competition between cycles, once-for-ever selective behaviour, utilization of small selective advantage, rapid evolvability, increased information capacity, and selection against parasitic branches.
The function of RNA is strongly dependent on its structure, so an appropriate recognition of this... more The function of RNA is strongly dependent on its structure, so an appropriate recognition of this structure, on every level of organization, is of great importance. One particular concern is the assessment of base-base interactions, described as the secondary structure, the knowledge of which greatly facilitates an interpretation of RNA function and allows for structure analysis on the tertiary level. The RNA secondary structure can be predicted from a sequence using in silico methods often adjusted with experimental data, or assessed from 3D structure atom coordinates. Computational approaches typically consider only canonical, Watson-Crick and wobble base pairs. Handling of non-canonical interactions, important for a full description of RNA structure, is still very difficult. We introduce our novel approach to assessing an extended RNA secondary structure, which characterizes both canonical and non-canonical base pairs, along with their type classification. It is based on predicti...
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Papers by Natalia Szostak