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- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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- Shrestha, R, et al.
(författare)
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Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status
- 2020
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 4:5, s. 845-854
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events in acute myeloid leukemia (AML) as well as in preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 mutations are infrequent in AML, but the level of TET3 expression in HSCs has been found to decline with age. We examined the impact of gradual decrease of TET function in AML development by generating mice with Tet deficiency at various degrees. Tet2f/f and Tet3f/f mice were crossed with mice expressing Mx1-Cre to generate Tet2f/wtTet3f/fMx-Cre+ (T2ΔT3), Tet2f/fTet3f/wtMx-Cre+ (ΔT2T3), and Tet2f/fTet3f/fMx-Cre+ (ΔT2ΔT3) mice. All ΔT2ΔT3 mice died of aggressive AML at a median survival of 10.7 weeks. By comparison, T2ΔT3 and ΔT2T3 mice developed AML at longer latencies, with a median survival of ∼27 weeks. Remarkably, all 9 T2ΔT3 and 8 ΔT2T3 mice with AML showed inactivation of the remaining nontargeted Tet2 or Tet3 allele, respectively, owing to exonic loss in either gene or stop-gain mutations in Tet3. Recurrent mutations other than Tet3 were not noted in any mice by whole-exome sequencing. Spontaneous inactivation of residual Tet2 or Tet3 alleles is a recurrent genetic event during the development of AML with Tet insufficiency.
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- Huang, Chien-Chung, 1976, et al.
(författare)
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A tight approximation bound for the stable marriage problem with restricted ties
- 2015
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Ingår i: Leibniz International Proceedings in Informatics, LIPIcs. - 1868-8969. - 9783939897897 ; 40, s. 361-380
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Konferensbidrag (refereegranskat)abstract
- © Chien-Chung Huang, Kazuo Iwama, Shuichi Miyazaki, and Hiroki Yanagisawa. The problem of finding a maximum cardinality stable matching in the presence of ties and unacceptable partners, called MAX SMTI, is a well-studied NP-hard problem. The MAX SMTI is NP-hard even for highly restricted instances where (i) ties appear only in women's preference lists and (ii) each tie appears at the end of each woman's preference list. The current best lower bounds on the approximation ratio for this variant are 1.1052 unless P=NP and 1.25 under the unique games conjecture, while the current best upper bound is 1.4616. In this paper, we improve the upper bound to 1.25, which matches the lower bound under the unique games conjecture. Note that this is the first special case of the MAX SMTI where the tight approximation bound is obtained. The improved ratio is achieved via a new analysis technique, which avoids the complicated case-by-case analysis used in earlier studies. As a by-product of our analysis, we show that the integrality gap of natural IP and LP formulations for this variant is 1.25. We also show that the unrestricted MAX SMTI cannot be approximated with less than 1.5 unless the approximation ratio of a certain special case of the minimum maximal matching problem can be improved.
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- Iwama, K, et al.
(författare)
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Max-stretch reduction for tree spanners
- 2005
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Ingår i: Algorithms and Data Structures / Lecture Notes in Computer Science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0302-9743 .- 1611-3349. - 9783540281016 ; 3608, s. 122-133
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Konferensbidrag (refereegranskat)abstract
- A tree t-spanner T of a graph G is a spanning tree of G whose max-stretch is t, i.e., the distance between any two vertices in T is at most t times their distance in G. If G has a tree t-spanner but not a tree (t - 1)-spanner, then G is said to have max-stretch of t. In this paper, we study the Max-Stretch Reduction Problem: for an unweighted graph G = (V, E), find a set of edges not in E originally whose insertion into G can decrease the max-stretch of G. Our results are as follows: (i) For a ring graph, we give a linear-time algorithm which inserts k edges improving the max-stretch optimally. (ii) For a grid graph, we give a nearly optimal max-stretch reduction algorithm which preserves the structure of the grid. (iii) In the general case, we show that it is NP-hard to decide, for a given graph G and its spanning tree of max-stretch t, whether or not one-edge insertion can decrease the max-stretch to t- 1. (iv) Finally, we show that the max-stretch of an arbitrary graph on n vertices can be reduced to s' >= 2 by inserting O(n/s') edges, which can be determined in linear time, and observe that this number of edges is optimal up to a constant.
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