Article
Biochemical Research Methods
Stefan Gerber, Gerhard Schratt, Pierre-Luc Germain
Summary: The diffUTR Bioconductor package simplifies and improves differential exon usage analysis, enabling differential 3' UTR usage analysis as well. It is more flexible and accurate than current state-of-the-art alternatives, facilitating DEU and exploration of their results.
BMC BIOINFORMATICS
(2021)
Article
Biochemical Research Methods
Minghao Jiang, Shiyan Zhang, Hongxin Yin, Zhiyi Zhuo, Guoyu Meng
Summary: RNA alternative splicing, a post-transcriptional stage, plays a crucial role in cellular homeostasis and disease. With the development of next-generation sequencing, detecting differential splicing from RNA-seq data has become mainstream. In this study, we evaluated 21 different tools based on simulated RNA-seq data, and observed significant discrepancies among them. We propose new methodological approaches and a protocol for selecting tools to improve the overall performance of differential splicing analysis.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Neurosciences
Serena Petry, Behnaz Nateghi, Remi Keraudren, Nicolas Sergeant, Emmanuel Planel, Sebastien S. Hebert, Isabelle St-Amour
Summary: This study investigates the alternative splicing of tau protein in HD patients and identifies abnormal splicing events in the putamen. Differences in exon 2 splicing coincide with increased tau hyperphosphorylation, aggregation, and markers of neurodegeneration, suggesting a potential biomarker or therapeutic target.
Article
Biochemistry & Molecular Biology
Dena Leshkowitz, Merav Kedmi, Yael Fried, David Pilzer, Hadas Keren-Shaul, Elena Ainbinder, Bareket Dassa
Summary: This study used three different sequencing platforms to explore global differential splicing during mouse embryonic stem cell differentiation, and analyzed the data using various bioinformatics strategies. The results showed that long-read sequencing was better at detecting differential splicing, while short-read sequencing was better at detecting differentially expressed genes. PCR validation confirmed differential exon usage in key differentiation genes.
Article
Biochemical Research Methods
Dingjie Wang, Xiufen Zou, Kin Fai Au
Summary: The study introduces a novel network-based analysis framework, Iso-Net, for predicting isoform-specific functions from exon-level RNA-Seq data, demonstrating its superior prediction accuracy and advantages.
Article
Computer Science, Information Systems
Kunj Bihari Meena, Vipin Tyagi
Summary: This paper proposes a new method for detecting and localizing image splicing forgery based on noise level estimation. The method utilizes techniques such as superpixel block division, PCA-based estimation, and k-means clustering. Experimental results show that the proposed method can accurately localize image splicing forgery compared to existing methods.
MULTIMEDIA TOOLS AND APPLICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Felix LaRoche-Johnston, Rafia Bosan, Benoit Cousineau
Summary: Group II introns are large self-splicing RNA enzymes that can generate mRNA chimeras through an intergenic trans-splicing pathway, increasing genetic diversity in bacterial hosts and producing new functional enzymes. Research has shown that some compound enzymes exhibit gain-of-function phenotypes, being more efficient than wild-type enzymes.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Agriculture, Multidisciplinary
F. Nikookalam Azim, A. A. Masoudi, A. Ehsani, R. Vaez Torshizi, P. Shariati Gazgazareh
Summary: Alternative splicing, transcript start site, and transcript polyadenylation site contribute to transcript diversity. This study analyzed the alteration process in sheep and goat breeds and its role in breed differentiation. RNA-seq data from ovarian tissue of different breeds were analyzed for differential exon usage. The results showed significant differences in exon usage between sheep breeds and goat breeds. Only a small percentage of exons were preserved between breeds, with the majority not exhibiting any alternatives. Alternative splicing was found to be the most influential type of alternative in sheep and goat breeds.
JOURNAL OF AGRICULTURAL SCIENCE AND TECHNOLOGY
(2023)
Article
Engineering, Electrical & Electronic
Xinchen Tao, Lei Peng, Yu Tao, Chaofeng Ye
Summary: The study focuses on a new flexible eddy current testing (ECT) probe for weld inspection, which has multiple modes to enhance sensitivity to different types of defects.
IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT
(2021)
Article
Biochemistry & Molecular Biology
Arfa Mehmood, Asta Laiho, Laura L. Elo
Summary: This study compared the performance of calling differentially expressed genes (DEGs) using read count data at different levels and showed that statistical testing at lower feature levels can improve DEG detection compared to traditional gene-level methods. The exon-level approach with empirical Brown's aggregation method achieved the best balance between accuracy and false discovery rate for detecting DEGs.
Article
Chemistry, Multidisciplinary
Thai Van Trinh, Son Trinh-Van, Kang-Yoon Lee, Youngoo Yang, Keum Cheol Hwang
Summary: This paper introduces a low-cost, low-sidelobe-level differential-fed substrate-integrated waveguide based slot array antenna with zero beam squint. The antenna utilizes differential feeding to achieve zero beam squint and tapered amplitude and in-phase excitation with the unequal power dividers, resulting in low cost and low sidelobe level.
APPLIED SCIENCES-BASEL
(2022)
Article
Automation & Control Systems
Chaofeng Ye, Na Zhang, Lei Peng, Yu Tao
Summary: This article proposes a new flexible probe for inspecting potential structural damages on curved surfaces of turbine blades. The probe has high sensitivity and reliability, and its performance is further improved through data fusion.
IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS
(2022)
Article
Chemistry, Analytical
Bo Du, Weijia Cui, Bin Ba, Haiyun Xu, Wubin Gao
Summary: The degree of freedom (DOF) is an important metric for evaluating sparse array designs in the field of DOA estimation. This paper proposes a novel L-shaped sparse sensor array that achieves higher degrees of freedom by adjusting the physical placement of sensors. The array consists of two sets of TSESAs, which estimate azimuth and elevation angles through 1-D spatial spectrum search. Simulation experiments demonstrate the superior performance of the proposed L-shaped TSESA in 2-D DOA estimation, due to its higher degrees of freedom and array aperture.
Article
Engineering, Electrical & Electronic
Yuhang Chen, Longfei Yan, Chong Han, Meixia Tao
Summary: Terahertz wireless communications aim to achieve data rates of over 100 Gbps for 6G communications using UM-MIMO systems and DAoSA beamforming technology. Challenges include precise DoA estimation, beam tracking, and reducing pilot overhead.
IEEE TRANSACTIONS ON WIRELESS COMMUNICATIONS
(2022)
Article
Environmental Sciences
Guo Zhao, Hao Huang, Ye Yu, Kun Zhao, Zhengwei Yang, Gang Chen, Yu Zhang
Summary: This study demonstrates the quantitative precipitation estimation (QPE) capability of X-band dual-polarization phased array radars (PAR) in Guangzhou, South China, and compares it with an S-band radar. Rainfall rate estimators based on specific differential phase (K-DP) were derived from raindrop size distributions observed by a 2-dimensional video disdrometer. The results showed that X-band PARs suffered more from attenuation than the S-band radar, leading to different estimated rainfall areas. However, the rainfall estimates from X-band PAR observations were more accurate than those from the S-band radar, especially in heavy precipitation areas.
Article
Multidisciplinary Sciences
Kalle T. Rytkonen, Thomas Faux, Mehrad Mahmoudian, Taija Heinosalo, Mauris C. Nnamani, Antti Perheentupa, Matti Poutanen, Laura L. Elo, Gunter P. Wagner
Summary: Trimethylation of histone H3 at lysine 4 (H3K4me3) plays a crucial role in marking active promoters in cells. This study investigates the dynamic changes of H3K4me3 in response to cellular stress, specifically hypoxia, in endometrial stromal cells. The findings reveal that hypoxia modifies existing H3K4me3 marks, and that the breadth of H3K4me3 domains, rather than their height, correlates with transcription activity. Broad H3K4me3 domains mark genes associated with endometrial core functions and are maintained or selectively extended upon hypoxia, suggesting their involvement in cellular stress adaptation.
Article
Biology
Anni S. Halkola, Tero Aittokallio, Kalle Parvinen
Summary: This study models the tumor microenvironment as a metapopulation to investigate the dynamics of cancer development at a single-cell level. The research reveals that angiogenesis promotes cancer cell growth, while anti-angiogenic treatment reduces the need for cytotoxic therapy. Interestingly, the model predicts that treatment resistance might become favorable to cancer cells when the anti-angiogenic treatment is intensive enough.
JOURNAL OF THEORETICAL BIOLOGY
(2022)
Article
Oncology
Weikaixin Kong, Liye He, Jie Zhu, Oscar Bruck, Kimmo Porkka, Caroline A. Heckman, Sujie Zhu, Tero Aittokallio
Summary: This study investigated the impact of combining pyroptosis- and immune-related genes on the prognostic classification of AML patients. By using a robust gene pairing method, an IPRP signature consisting of 15 genes was developed. The results demonstrate that the IPRP score predicts survival more consistently and accurately compared to other existing signatures. Additionally, the IPRP scoring is widely applicable to different patient cohorts, treatment procedures, and transcriptomic technologies.
Article
Nutrition & Dietetics
Anniina Keskitalo, Eveliina Munukka, Anna Aatsinki, Wisam Saleem, Noora Kartiosuo, Leo Lahti, Pentti Huovinen, Laura L. Elo, Sami Pietila, Suvi P. Rovio, Harri Niinikoski, Jorma Viikari, Tapani Ronnemaa, Hanna Lagstrom, Antti Jula, Olli Raitakari, Katja Pahkala
Summary: This study investigated the impact of long-term dietary counseling on gut microbiota, finding higher abundance of Veillonella genus bacteria in the intervention group and an association between the study group and overall gut microbiota profile only in males.
Article
Multidisciplinary Sciences
Oxana Denisova, Joni Merisaari, Amanpreet Kaur, Laxman Yetukuri, Mikael Jumppanen, Carina Von Schantz-Fant, Michael Ohlmeyer, Krister Wennerberg, Tero Aittokallio, Mikko Taipale, Jukka Westermarck
Summary: Therapeutic resistance to kinase inhibitors, particularly in glioblastoma, is a major challenge in cancer treatment. Researchers have developed an actionable targets of multi-kinase inhibitors (AToMI) strategy to identify target kinases involved in the therapeutic effects of multi-kinase inhibitors. Using this strategy, they successfully characterized AKT and mitochondrial pyruvate dehydrogenase kinase PDK1 and PDK4 as target kinases of staurosporine derivatives that synergized with PP2A activation in glioblastoma cells.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Astrid Murumagi, Daniela Ungureanu, Suleiman Khan, Mariliina Arjama, Katja Valimaki, Aleksandr Ianevski, Philipp Ianevski, Rebecka Bergstrom, Alice Dini, Anna Kanerva, Riitta Koivisto-Korander, Johanna Tapper, Heini Lassus, Mikko Loukovaara, Andrus Magi, Akira Hirasawa, Daisuke Aoki, Vilja Pietiainen, Teijo Pellinen, Ralf Butzow, Tero Aittokallio, Olli Kallioniemi
Summary: Efforts are being made to develop new therapies for aggressive high-grade serous ovarian cancers (HGSOCs), but the understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) ovarian malignancies is lacking. A functional precision oncology (fPO) strategy combining drug testing, genomic profiling and transcriptomic profiling was used to study epithelial ovarian cancers (EOC). Different drug response profiles were observed among HGSOC, LGSOC, and MUCOC PDCs, with LGSOCs responding better to targeted inhibitors. Specific drug responses were identified for each subtype, with potential for individualized therapies in the future.
BRITISH JOURNAL OF CANCER
(2023)
Review
Oncology
Timothy Johanssen, Laura McVeigh, Sara Erridge, Geoffrey Higgins, Joelle Straehla, Margaret Frame, Tero Aittokallio, Neil O. Carragher, Daniel Ebner
Summary: Glioblastoma (GBM) is a cancer with high unmet clinical need. Traditional drug discovery methods have failed to overcome the challenges presented by tumor heterogeneity, therapeutic resistance, and tumor niches. Academic researchers are now implementing high throughput screening programs to identify novel combination targets for GBM by using more relevant phenotypic assays and focused libraries of small compounds. Recommendations are made to improve the preclinical small compound screening paradigm for better identification of tractable combinatorial inhibitors and drug targets specific to GBM.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Astrid Oras, Henna Kallionpa, Tomi Suomi, Satu Koskinen, Asta Laiho, Laura L. Elo, Mikael Knip, Riitta Lahesmaa, Alar Aints, Raivo Uibo
Summary: A study on the gene expression in B-cells from children developing CoD early in life revealed gene expression changes associated with CoD development, indicating the important role of B-cells in CoD development.
Review
Oncology
Laszlo Lorenzovici, Laszlo Szilberhorn, Szabolcs Farkas-Raduly, Andrea Ildiko Gasparik, Andreea Mihaela Precup, Adel Gyongyver Nagy, Carsten Utoft Niemann, Tero Aittokallio, Zoltan Kalo, Marcell Csanadi
Summary: This study conducted a systematic literature review to summarize the health economic models related to CLL therapies. The review found that Markov modeling is commonly used to simulate cost effectiveness, but recent studies have added more complexity to the models.
Article
Biochemistry & Molecular Biology
Swapnil Potdar, Filipp Ianevski, Aleksandr Ianevski, Ziaurrehman Tanoli, Krister Wennerberg, Brinton Seashore-Ludlow, Olli Kallioniemi, Paeivi Ostling, Tero Aittokallio, Jani Saarela
Summary: Functional precision medicine (fPM) simplifies the search for appropriate applications of existing molecules and enhances therapeutic potential. The latest version of Breeze (release 2.0) provides advanced data exploration capabilities and interactive visualization options for accurate interpretation of drug sensitivity and resistance data. It allows integration and cross-comparison of user-uploaded data with publicly available drug response datasets.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Anni S. S. Halkola, Kaisa Joki, Tuomas Mirtti, Marko M. M. Maekelae, Tero Aittokallio, Teemu D. D. Laajala
Summary: This paper presents a novel methodology for feature subset selection based on the L-0 pseudonorm, which has advantages in clinical applicability, selection of grouped features, and analysis of high-dimensional transcriptomics data. The methodology is benchmarked against existing regularization methods and shows superior performance.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Oncology
Moritz Otte, Johanna Stachelscheid, Markus Glass, Linus Wahnschaffe, Qu Jiang, Waseem Lone, Aleksandr Ianevski, Tero Aittokallio, Javeed Iqbal, Michael Hallek, Stefan Huettelmaier, Alexandra Schrader, Till Braun, Marco Herling
Summary: T-prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Elevated expression of miR-141/200c cluster in T-PLL cells promotes cell proliferation and alters the expression of genes involved in cell survival and differentiation. Low expression of STAT4, a target gene of miR-141/200c, is associated with an immature phenotype of T-PLL cells and shortened overall survival of T-PLL patients. This study reveals the oncogenic role of miR-141/200c-STAT4 signaling pathway in T-PLL, shedding light on the involvement of non-protein-coding genes in the pathogenesis of this devastating disease.
Review
Oncology
Mona Meng Wang, Sarah E. Coupland, Tero Aittokallio, Carlos R. Figueiredo
Summary: Immune checkpoint therapies can enhance the function of anti-tumour T cells and improve outcomes in cancer patients. However, some patients are refractory to this therapy due to "cold" tumours that do not allow T cell generation or the infiltration of existing anti-tumour T cells. This review explores the mechanisms by which cancer cells induce T cell "desertification" and "exclusion" in these refractory tumours, and highlights the importance of developing immunotherapies that restore T cell generation and tumour trafficking.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Oxana V. Denisova, Joni Merisaari, Riikka Huhtaniemi, Xi Qiao, Laxman Yetukuri, Mikael Jumppanen, Amanpreet Kaur, Mirva Paakkonen, Carina von Schantz-Fant, Michael Ohlmeyer, Krister Wennerberg, Otto Kauko, Raphael Koch, Tero Aittokallio, Mikko Taipale, Jukka Westermarck
Summary: Mitochondrial glycolysis and hyperactivity of the AKT pathway are characteristic of brain tumors, but targeting AKT or PDK has shown limited clinical benefits. In this study, a triplet therapy targeting AKT, PDK, and PP2A was effective in inducing apoptosis in brain tumor cells. Reactivating PP2A converted the cytostatic response to cytotoxic apoptosis by shutting down compensatory mitochondrial oxidative phosphorylation. These findings suggest the potential of targeting mitochondrial metabolism to overcome therapy tolerance in brain tumors.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Paschalis Athanasiadis, Balaguru Ravikumar, Richard J. R. Elliott, John C. Dawson, Neil O. Carragher, Paul A. Clemons, Timothy Johanssen, Daniel Ebner, Tero Aittokallio
Summary: Designing a targeted screening library of bioactive small molecules is a challenging task due to the complexity of compound-protein interactions. In this study, we developed analytic procedures to design anticancer compound libraries that consider factors such as library size, cellular activity, chemical diversity, and target selectivity. The resulting compound collections cover a wide range of protein targets and biological pathways implicated in various cancers, making them valuable for precision oncology. In a pilot screening study, we identified patient-specific vulnerabilities using a physical library of compounds, highlighting the heterogeneity of phenotypic responses across patients and glioblastoma subtypes.
