02189nas a2200181   4500008004100000022001400041245010700055210006900162260007200231300001400303490000700317520147000324100002401794700001701818700002101835700002301856856012801879       2013                        eng d  a0305-104800aOne size does not fit all: on how markov model order dictates performance of genomic sequence analyses0 aOne size does not fit all on how markov model order dictates per  aGREAT CLARENDON ST, OXFORD OX2 6DP, ENGLANDbOXFORD UNIV PRESScFEB  a1416-14240 v413 a<p>The structural simplicity and ability to capture serial correlations make Markov models a popular modeling choice in several genomic analyses, such as identification of motifs, genes and regulatory elements. A critical, yet relatively unexplored, issue is the determination of the order of the Markov model. Most biological applications use a predetermined order for all data sets indiscriminately. Here, we show the vast variation in the performance of such applications with the order. To identify the `optimal' order, we investigated two model selection criteria: Akaike information criterion and Bayesian information criterion (BIC). The BIC optimal order delivers the best performance for mammalian phylogeny reconstruction and motif discovery. Importantly, this order is different from orders typically used by many tools, suggesting that a simple additional step determining this order can significantly improve results. Further, we describe a novel classification approach based on BIC optimal Markov models to predict functionality of tissue-specific promoters. Our classifier discriminates between promoters active across 12 different tissues with remarkable accuracy, yielding 3 times the precision expected by chance. Application to the metagenomics problem of identifying the taxum from a short DNA fragment yields accuracies at least as high as the more complex mainstream methodologies, while retaining conceptual and computational simplicity.</p>1 aNarlikar, Leelavati1 aMehta, Nidhi1 aGalande, Sanjeev1 aArjunwadkar, Mihir  uhttps://library.ncl.res.in/content/one-size-does-not-fit-all-how-markov-model-order-dictates-performance-genomic-sequence-002543nas a2200253   4500008004100000022001400041245005900055210005900114260000800173300001200181490000700193520177800200100002301978700001802001700002102019700001702040700001902057700002602076700002402102700002602126700002302152700002002175856009402195       2021                        eng d  a1088-905100aOrc4 spatiotemporally stabilizes centromeric chromatin0 aOrc4 spatiotemporally stabilizes centromeric chromatin  cAPR  a607-6210 v313 a<p>The establishment of centromeric chromatin and its propagation by the centromere-specific histone CENPA is mediated by epigenetic mechanisms in most eukaryotes. DNA replication origins, origin binding proteins, and replication timing of centromere DNA are important determinants of centromere function. The epigenetically regulated regional centromeres in the budding yeast Candida albicans have unique DNA sequences that replicate earliest in every chromosome and are clustered throughout the cell cycle. In this study, the genome-wide occupancy of the replication initiation protein Orc4 reveals its abundance at all centromeres in C. albicans. Orc4 is associated with four different DNA sequence motifs, one of which coincides with tRNA genes (tDNA) that replicate early and cluster together in space. Hi-C combined with genome-wide replication timing analyses identify that early replicating Orc4-bound regions interact with themselves stronger than with late replicating Orc4-bound regions. We simulate a polymer model of chromosomes of C. albicans and propose that the early replicating and highly enriched Orc4-bound sites preferentially localize around the clustered kinetochores. We also observe that Orc4 is constitutively localized to centromeres, and both Orc4 and the helicase Mcm2 are essential for cell viability and CENPA stability in C. albicans. Finally, we show that new molecules of CENPA are recruited to centromeres during late anaphase/telophase, which coincides with the stage at which the CENPA-specific chaperone Scm3 localizes to the kinetochore. We propose that the spatiotemporal localization of Orc4 within the nucleus, in collaboration with Mcm2 and Scm3, maintains centromeric chromatin stability and CENPA recruitment in C. albicans.</p>1 aSreekumar, Lakshmi1 aKumari, Kiran1 aGuin, Krishnendu1 aBakshi, Asif1 aVarshney, Neha1 aThimmappa, Bhagya, C.1 aNarlikar, Leelavati1 aPadinhateeri, Ranjith1 aSiddharthan, Rahul1 aSanyal, Kaustuv  uhttps://library.ncl.res.in/content/orc4-spatiotemporally-stabilizes-centromeric-chromatin