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Everything You Care about Hi-C in 2017 Is Here

2018.02.06

At the beginning of 2017, you may still be learning about what is Hi-C, and by the end of the year, the feedback about the articles of genome you may receive is to assemble the chromosome to get genome of chromosome level. Meanwhile, with the pity of failing to construct mapping population, you find out that Hi-C is not to be neglected, don’t you?


When you look back the countless published articles of genome in 2017, you will find out that Hi-C has played an irreplaceable role in the genome assembly - to assist the assembly of genome to get genome of chromosome level. According to current incomplete articles of genome in the following table, Hi-C would eventually become the classic method for genome assembly.


Tab. 1 Articles about Hi-C

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If you think that these articles are not enough to show the significance and necessity of Hi-C in genome assembly, I’m going to summarize the questions you concerned about and the articles as follows, to throw out a minnow to catch a whale.


Ø    Reference genome of chromosome level


When you look up the assembly level of genome in NCBI, you may find three different assembly levels: contig, scaffold and chromosome. For different levels, the available analysis based on the genome is also different. It is generally recommended to assemble the genome to get genome of chromosome level, for the reference genome of chromosome level is the basic requirement for numerous analyses.


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Fig. 1 Necessity of Reference Genome of Chromosome Level


These are just analyses related to genomics. In fact, analysis related to epigenetics (e.g. whole genome methylation sequencing) also regards the reference genome of chromosome level as an essential condition. Therefore, it is genome of chromosome level that is the ladder for follow-up study and publication.


Ø    Evaluation of assembly results


Generally, the results of assembly can be illustrated by mounting rate (the proportion of the length of mounted version in draft assembly). Currently, all projects of Annoroad have achieved an average mounting rate of over 90%, and some projects even have a mounting rate of over 98%. However, it is relatively shallow to evaluate the effect of assembly simply by comparing the data before and after being mounted. It can be inferred from the already published articles that, more evaluations intend to carry out consistency analysis on the versions before and after being assembled with genetic map. And the fact is that, currently, Annoroad Gene can not only carry out the above analyses, but also adopt the following methods to evaluate the results of assembly:


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Fig. 3 Evaluation Methods for the Results of Hi-C Genome Assembly


Different evaluation methods can show the effect of assembly from different aspects. And interaction heat map is the most common and intuitive one.


Ø    Assembly error correction


If assembly can not only realize the scaffolding of chromosome level, but also correct certain errors in draft assembly, it will significantly improve the quality of current genome assembly and reduce errors in assembly. In 2017, Dudchenko O. et al. put forward to add error correction analysis  based on existing assembly policy, and realized assembly after correction of draft genome by 3d-dna. However, the correction function wasn’t applied well due to the limited universality of this software. Currently, Annoroad Gene has optimized the analysis process based on a piece of common software named LACHESIS, and successfully realized the function of correction in Hi-C. Meanwhile, the assembly effect of practical project has greatly improved after error correction.


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Fig. 4 Comparison between Heat Maps of Hi-C before and after Error Correction


Hi-C 3D Genome Sequencing Technique


Innovations:


As the leader of 3D genome sequencing technique, Annoroad Gene continues to improve Hi-C sequencing, perfect the content of Hi-C analysis, and devotes itself to providing Hi-C sequencing service with best quality and highest cost performance for vast science researchers. In 2017, Annoroad has upgraded its Hi-C in database construction, sequencing and analysis with continuous innovation. Annoroad has broken through significant technological difficulties and realized sharp decrease of sequencing data size, increase of success rate of database construction and effective utilization of data, comprehensive improvement of the content of multi-group conjoint analysis, and other important technical progresses.


Ø    Advancing Annoroad Hi-C

In 2017, Annoroad not only broke through the technological difficulties in database construction and sequencing, which significantly reduced the data size of sequencing and continually increased the success rate of database construction and effective utilization of data, but also greatly upgraded the process of Hi-C analysis as follows:


1) Optimize the analysis process of LACHESIS to enable this software to apply to the draft assemblies of different assembly levels, and obviously improve the effect of assembly, to yield real chromosome-length scaffold, which is the reference genome of chromosome level. And compare the published articles while displaying the results and add result statistics after assembly to better display the effect;


2) Evaluate the results of multi-level assemblies, regard the evaluation on interaction heat map as the standard analysis, and provide the colinearity analysis, consistency analysis and accuracy analysis based on the practical project as personalized analysis;


3) Add analysis on error correction of assembly to the analysis process of LACHESIS, to provide a strong help to genome assembly.


Of course, we won’t stop here. We will add more practical analyses in the analysis on Hi-C results later, including the location prediction of special structure of chromosome, to better serve people. You may look forward to it.