Most of the conventional feature selection algorithms have a drawback whereby a weakly ranked gene that could perform well in terms of classification accuracy with an appropriate subset of genes will ...be left out of the selection. Considering this shortcoming, we propose a feature selection algorithm in gene expression data analysis of sample classifications. The proposed algorithm first divides genes into subsets, the sizes of which are relatively small (roughly of size h), then selects informative smaller subsets of genes (of size r <; h) from a subset and merges the chosen genes with another gene subset (of size r) to update the gene subset. We repeat this process until all subsets are merged into one informative subset. We illustrate the effectiveness of the proposed algorithm by analyzing three distinct gene expression data sets. Our method shows promising classification accuracy for all the test data sets. We also show the relevance of the selected genes in terms of their biological functions.
Open source clustering software de Hoon, M.J.L.; Imoto, S.; Nolan, J. ...
Bioinformatics,
06/2004, Letnik:
20, Številka:
9
Journal Article
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We have implemented k-means clustering, hierarchical clustering and self-organizing maps in a single multipurpose open-source library of C routines, callable from other C and C++ programs. Using this ...library, we have created an improved version of Michael Eisen's well-known Cluster program for Windows, Mac OS X and Linux/Unix. In addition, we generated a Python and a Perl interface to the C Clustering Library, thereby combining the flexibility of a scripting language with the speed of C. Availability: The C Clustering Library and the corresponding Python C extension module Pycluster were released under the Python License, while the Perl module Algorithm::Cluster was released under the Artistic License. The GUI code Cluster 3.0 for Windows, Macintosh and Linux/Unix, as well as the corresponding command-line program, were released under the same license as the original Cluster code. The complete source code is available at http://bonsai.ims.u-tokyo.ac.jp/~mdehoon/software/cluster. Alternatively, Algorithm::Cluster can be downloaded from CPAN, while Pycluster is also available as part of the Biopython distribution.
Metastasis is a critical factor contributing to poor prognosis in cancer, but the underlying mechanisms of metastasis are still poorly understood. We established a highly metastatic cell subline ...(HOC313-LM) derived from an oral squamous cell carcinoma cell line (HOC313) for uncovering the mechanisms of metastasis, and identified deoxyhypusine synthase (DHPS) as a metastasis-associated gene within the specific amplification at 19p13.2-p13.13 in HOC313-LM. DHPS-mediated hypusine-modification of eukaryotic translation factor 5A facilitated the translation of RhoA, resulting in the activation of the RhoA signaling pathway and leading to not only increased cell motility, invasion and metastasis of cancer cells in vitro, but also increased tumor growth in vivo. Moreover, the use of N1-Guanyl-1,7-diaminoheptane, a DHPS inhibitor, resulted in a significant decrease in tumor formation in vivo. In patients with esophageal squamous cell carcinoma (ESCC), overexpression of DHPS in ESCC tumors was significantly associated with worse recurrence-free survival, and correlated with distant metastasis. The elucidation of these molecular mechanisms within the hypusine cascade suggests opportunities for novel therapeutic targets in SCC.
Abstract
During the COVID-19 pandemic, it has been important to both minimize the risk of infection and restore daily life. As a typical example, mass gathering events, such as sporting events, are ...gradually becoming more common, thanks to the measures taken to contain COVID-19. Some pilot studies have been launched at governments’ initiative to investigate the risk of infection without measures such as face masks and physical distancing at mass gathering events, but the ethics of these studies should be carefully considered. On the other hand, it is still beneficial to implement infection control measures at mass gathering events and, in parallel, to estimate the risk of infection with measures in place, especially under a lack of vaccination progress or the spread of mutant strains possibly resistant to vaccines. To help improve compliance with measures taken by spectators and organizers and to ensure their effectiveness, we have conducted quantitative evaluations of the implementation of such measures by monitoring CO2 concentrations, assessing the proportion of people wearing face masks and analysing human flow at the event. This approach allows us to share our observations with stakeholders and participants, enabling us to protect the culture of mass gathering events, minimize the risk of infection and restore a sense of well-being in daily life.
Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains ...the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation.
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized with chromosomal instability and a high propensity to myeloid malignancy. Although causative genes have been identified ...in most patients, the genetic background of the leukemic transformation in FA has not been fully understood.
We studied 2 acute myeloid leukemia (AML) and 7 myelodysplastic syndromes (MDS) developed in patients with FA using whole-genome sequencing and analyzed somatic mutations, structural variants and copy number alterations.
The number of somatic mutations and copy number alterations (CNAs) in AML were 1,071 mutations and 4 CNAs per patient on average, which tended to be higher than those in MDS (265 mutations and 2.3 CNAs per patient). For mutational signatures, three known signatures were identified, which included SBS1 and SBS5 caused by endogenous mutational processes, and SBS3 related to defective homologous recombination. Mutations and structural variants affected known driver genes in myeloid malignancies, such as RUNX1 (n = 3), ASXL1 (n = 1), CBL (n = 1), NRAS (n = 1) and KDM6A (n = 1). Recurrent copy number alterations were more frequently detected, including +3q (n = 6), +1q (n = 4) and -7q (n = 2). The majority of these CNAs were clonal and all but one patient harbored either of +3q or +1q, indicating the early acquisition of copy number changes and their driver role in leukemic transformation.
Myeloid neoplasms related with FA were characterized by a unique pattern of CNAs and common driver mutations in myeloid malignancies.
Pulmonary thromboembolism is a potentially life‐threatening disorder, which can occur secondary to deep vein thrombosis. Ovarian vein thrombosis has classically been considered to be a postpartum ...complication and is less frequently associated with other disease processes, such as recent pelvic surgery. Herein, we report a case of pulmonary thromboembolism as a result of ovarian vein thrombosis in a 39‐year‐old woman after an uneventful laparoscopic‐assisted vaginal hysterectomy for uterine myoma. On postoperative day 3, the patient experienced fever of unknown origin, followed by lower abdominal pain, chest discomfort and shortness of breath. A hematological examination revealed an elevated D‐dimer level. Computerized tomography revealed pulmonary thromboembolism caused by left ovarian vein thrombosis. The administration of anticoagulants resolved the symptoms. In order to avoid significant morbidities and potential mortality, attention should be paid to the possibility of pulmonary thromboembolism resulting from ovarian vein thrombosis, even after minimally invasive gynecologic surgery for benign conditions.
Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with ...microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder.
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