Tuesday, January 14, 2014

GRCh38: Incorporating Modeled Centromere Sequence

Centromeres are specialized chromatin structures that are required for cell division. The composition of these regions is complex, as they are made up of a series of tandem repeats that are arranged into nearly identical multi-megabase arrays. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. The Human Genome Project (HGP) employed a clone based strategy (largely BAC clones) to produce the reference assembly, but cloning centromere sequences generally requires special effort, and isn't readily applicable to all human centromeres (see Kouprina et al., 2003 for one such effort). With the recent widespread adoption of whole genome sequencing (WGS), there are clearly alpha-satellite sequences in the reads produced, but assembling these sequences into faithful representations of centromeres using standard techniques is impossible due to the repetitive nature of these sequences. In all previous versions of the human reference assembly, the centromere regions have been represented by a 3 Mb gap (that is a stretch of 3 million Ns). Recent efforts by Karen Miga and her colleagues are helping us improve centromere representation in the reference assembly. The GRCh38 reference assembly incorporates centromere models created by Miga and colleagues, along with their modeled region of one of the heterochromatic regions on the long arm of chromosome 7. These models replace the multi-megabase gaps that are in GRCh37.

As described in Miga et al., 2013,  Karen and her colleagues used the whole genome shotgun (WGS) reads that were generated as part of the Venter sequencing project (Levy, et al., 2007) to build centromere models (Fig.1). They started by identifying sequence reads containing alpha-satellite centromere sequences. They then used these reads to construct models representing the approximate repeat number and order for each of the centromeric alpha-satellite higher order arrays in the genome. Because there are two copies of each centromere for each autosome, these centromere models represent an average of the two centromere copies. On the acrocentric chromosomes, where there is extreme inter-chromosomal array sequence homogeneity, the array models found in GRCh38 include data from all four acrocentric regions. The team was also able to use read pair information to link the modeled scaffold arrays to the adjacent euchromatic sequence present in the Venter assembly.
Fig. 1
Schematic of modeled centromere sequence. Centromeres are comprised of higher order array sequences, which consist of alpha-satellite interrupted by various repeat elements (such as SINE or LINE elements), and inter-array (euchromatic) sequences.
The model centromere sequences are not exact representations of the centromeres found in the Venter genome. The sequence diversity and complexity of these regions make constructing the exact copies of each centromere with current sequencing technologies impossible. Each model represents variants and monomer ordering in a proportional manner to that observed in the initial read database, but the long-range ordering of the repeats and ordering of the linked euchromatic contigs represents only an inferred sequence. However, inclusion of these models in the reference assembly will be beneficial for the research community. Even for those not interested in centromere biology, it is likely that inclusion of these models will improve overall read alignments in individual re-sequencing efforts. Reads containing centromeric sequences are generated in whole genome sequencing experiments and providing an alignment target for these reads will reduce the number of off target alignments and unaligned reads. For those interested in centromere biology, Karen and her colleagues provide evidence in their manuscript that these models can be used to study sequence diversity in these regions.

55 comments:

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  30. Hello Am From The UK , I want to write a little testimony about the good work of doctor Oyagu who cured me from Hsv 1 and 2 for just 2 weeks with his herbal medicine, I never believe I can be normal again and have a good life like others I always regretted the day I got diagnose with the virus, I was lost of hope when my doctor told me there is no cure for it but I keep thinking and thinking about my future, if I can have kids of my own well I am so grateful for my helper who get me cured with his herbal medicine, I go online in search of anything that can help me because I can’t deal with it forever so I found this doc Oyagu email on a blog of someone who was cured by him I quickly contact him for help and explain all my pain to him, he told me not to worry about it there is cure for real, I never believe until he send me the herbal medicine when I order for it and I have it within 4 days that is how I took the medicine for 2 week and the following week I go for test just to confirm I was 100% cured from this sickness what a miracle in my life I am so happy right now, you can also get in contact with him if you have such sickness through email address oyaguherbalhome@gmail.com or text him on whatasApp , phone number +2348101755322 or visit his website https://oyaguspellcaster.wixsite.com/oyaguherbalhome if you are infected with HERPES virus or having any health problems you can contact Dr Oyagu and he will help you.

    ReplyDelete
  31. I am so Happy to be writing this article in here, i am here to explore blogs forum about the wonderful and most safe cure for HERPES SIMPLEX VIRUS . I was positive to the deadly Virus called HERPES and i lost hope completely because i was rejected even by my closet friends. i searched online to know and inquire about cure for HERPES and i saw Dr.USELU testimony online on how he was cured so many persons from Herpes Disease so i decided to contact the great herbalist because i know that nature has the power to heal everything. i contacted him to know how he can help me and he told me never to worry that he will help me with the natural herbs from God! after 2 days of contacting him, he told me that the cure has been ready and he sent it to me via FEDEX or DHL and it got to me after 4 days! i used the medicine as he instructed me (MORNING and EVENING) and i was cured! its really like a dream but i’m so happy! that’s the reason i decided to also add more comment of Him so that more people can be saved just like me! and if you need his help,contact his Email:(dr.uelucaregvier@gmil.com) you can contact him on WHTASAPP +2347052898482 He said have the herb to cure difference cure for any sickness  https://druseluherbalhome.simdif.com/
    (1) HERPES,
    (2) DIABETES,
    (3) HIV&AIDS,
    (4) URINARY TRACT INFECTION,
    (5) HEPATITIS B,
    (6) IMPOTENCE,
    (7) BARENESS/INFERTILITY
    (8) DIARRHEA
    (9) ASTHMA… AND MORE

    ReplyDelete
  32. I think this is one of the most significant information for me. And i am glad reading your article. But want to remark on some general things, The website style is perfect, the articles is really great : D. Good job, cheers

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    ReplyDelete
  33. Greetings to the general public, I want to tell about how I was cured of
    HIV disease by a Doctor called Dr. voodoo . I was browsing the Internet
    searching for remedy on HIV and I saw a comment of people talking about how
    Doctor voodoo cured them. I was scared because I never believed in the
    Internet but i was convince to give him a try because i having no hope of
    been cured of HIV so I decided to contact him with his email that was
    listed on the comment voodoospelltemple66@gmail.com when I contacted
    him he gave me hope and send a Herbal medicine to me that I took and
    it seriously worked for me, am a free person now without problem,
    my HIV result came out negative. I pray for you Dr. voodoo God will give
    you everlasting life, you shall not die before your time for being sincere
    and great men. Am so happy, you can also contact him if you have any
    problem Email: voodoospelltemple66@gmail.com
    or Add him up on WhatsAp +2348140120719

    ReplyDelete
  34. Hi everyone, i want to thank Dr Graceondu for praying for me and giving me a lottery game that changed my life, i have been playing lottery game for a very long time but never win big, i contact Dr Graceondu online after reading some testimonies about him, He prayed for me and gave me a lottery number which i played, and for that first time i won a big amount. I also want you to contact him for your lucky game.
    You can reach him through his Email at drgraceondu12@gmail.com, or WhatsApp him +15204677763

    ReplyDelete
  35. It’s obvious some patient with HERPES are been enslaved to the antiviral and other supplementary Orthodox medicine just to help suppress the virus and not a cure. I have been with the virus since 2020 until I was introduce by a blogger who also narrated Her story online on how she was cured of Herpes after using Dr ISHIAKU Herbal Medicine. This is a year and 2 weeks since I was delivered from Herpes. All thanks to God for using this Great herbalist to heal me. I have promise to keep telling good about this. Please fill free to share Your problems with him. Thanks. Write him via call or whatsapp him on +2348180828544 or email ishiakuherbalcure@yahoo.com thank you once again sir

    ReplyDelete
  36. Hi everyone i want to share my amazing testimony on how Dr Graceondu blessed my life, i used to work as a cleaner in supper market, i have been playing lottery game for long now and i don't usually win, i came across a testimony of someone testifying about how Dr Graceondu prayed for her and gave her a lottery game to play and she won big amount of money, so i also decided to try my luck, i contact him through his website and he assured me that he will help me, he told me it will take him two day to pray for me, so on the second day he gave me some lottery numbers to play and i went to play the game so on that faithful day i went to check the game to my greatest surprise i won a very big amount $234.2 million that changed my life and my status, i quit working as a cleaner in the supper market and i became a company owner.
    I want you out there to also contact him for your lucky game.
    You can reach him via his Email drgraceondu12@gmail.com or WhatsApp him on +15204677763
    you can also visit his website at https://drgraceonduadodo.com

    ReplyDelete
  37. Getting rib of Herpes virus wasn't easy, I came across Dr voodoo on how he
    has cured so many people from herpes and other illness so I decided to give
    him a try, now am permanently cured using the natural herbs medication and
    cleansing supplement sent by Dr voodoo no more herpes, contact Dr voodoo
    WhatsApp number +2348140120719 also e-mail him at:
    voodoospelltemple66@gmail.com

    ReplyDelete