ESHG 2016 is running

The annual meeting of the Europea Society of Human Genetics is currently running in Barcelona. Follow on Twitter (#ESHG2016) us and other researchers from all across Europe as we share amazing new science and technology.

There are exomes in Brescia!

Finally, after about two years of sequencing, our small lab was able to publish a little contribution to the world of exome sequencing. In the paper we performed a detailed evaluation of exome sequencing performances and technical optimizations using the Ion Proton platform with the Hi-Q chemistry.
No more than a drop in the ocean, but we are quite proud of it!

The article is published in open-access so everyone interested can take a look!

Amplicon-based semiconductor sequencing of human exomes: performance evaluation and optimization strategies
E.Damiati, G.Borsani, E.Giacopuzzi
Human Genetics, May 2016, Volume 135, Issue 5, pp 499-511

Resilience project identifies the first 13 genetic heroes!

The Resilience Project has just published on Nature Biotechnology a new paper on the analysis of genomic data from more than 500k subjects in search for the so called "genetic heroes". The authors first aggregated genomic data from various sources, including 23andMe genotyping database, 1000G, ESP6500 and UK10K sequencing projects, Sweden exomes for schizophrenia research, CHOP sequencing program and others, to reach a total of 589,306 subjects with genomic data. Then they applied a strict filtering criteria to identify 13 healthy people bearing a pathogenic mutations for severe Mendelian childhood disease without showing any clinical symptoms.

Analyzing genomic data from these 13 "genetic heroes" the authors are now trying to study protective variants to understand the molecular mechanisms that have rescued the pathogenic mutations, with the potential to provide useful insight on how to treat the corresponding disease.

Recent interesting facts in genomics!

Human genetic knockouts point to a resilient human genome

According to this paper published in Science, the human genome is more resilient than previously expected and can tolerate a certain amount of disrupted genes without any observable phenotypic effect. The authors "sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. [...] Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate.".
Interested? Read the full paper: "Health and population effects of rare gene knockouts in adult humans with related parents"

Genetic alterations in regulatory elements could predict personal health history

This paper published on PLoS Computational Biology analyze the impact of personal genetic variants on conserved regulatory elements and how this information could be used to predict health related traits. By analyzing transcription factor binding sites disrupted by an individual’s variants and then look for their most significant congregation next to a group of functionally related genes, the authors found that the top enriched function is invariably reflective of medical histories. As stated by authors these "results suggest that erosion of gene regulation by mutation load significantly contributes to observed heritable phenotypes that manifest in the medical history". They also developed a computational test to interpret personal genomes based on their approach that "promise to shed new light on human disease penetrance, expressivity and the sensitivity with which we can detect them".
Interested? Read the full paper: "Erosion of Conserved Binding Sites in Personal Genomes Points to Medical Histories"

Don't forget about exonic splice-affecting mutations

In this interesting paper on PLoS Genetics authors evaluate the prevalence of splice-affecting exonic variants. This kind of variants are often neglected in the canonical pipelines searching for causative mutations, even if aberrant splicing can obviously have a major impact on gene function. Using MLH1 as a model gene, the authors found that the frequency of this kind of mutations is higher than expected, suggesting that they deserve more attention in future analysisi. Moreover the paper also provide with a comparative evaluation of different in silico prediction alghoritms assessing their performance in splice-affecting variants classification.
Interested? Read the full paper: "Exonic Splicing Mutations Are More Prevalent than Currently Estimated and Can Be Predicted by Using In Silico Tools"

The health impact of your Neanderthal ancestry

Another interesting story published recently on Science journal pointed out the influence of Neanderthal ancestry on human health-related traits. The authors analyzed how alleles inherited from Neanderthals in present European population impact clinically relevant phenotypes and they found associations for neurological, psychiatric, immunological, and dermatological phenotypes. The results indicate that archaic admixture influences disease risk in modern humans, including risk for depression and skin lesions resulting from sun exposure, hypercoagulation and tobacco use.
Interested? Read the full paper: "The phenotypic legacy of admixture between modern humans and Neandertals"

A map of transciptomic cellular landscape in visual cortex by single cell RNA-Seq

This study from Nature Neuroscience used single cell RNA-Seq on more than 1,600 cells to construct a cellular taxonomy of the primary visual cortex in adult mice. Authors identified 49 transcriptomic cell types, displaying specific and differential electrophysiological and axon projection properties, confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties. These results open new perspective on cell level organization within brain tissue, first of all on the potential causal relationships between transcriptomic signatures and specific morphological, physiological and functional properties. Another interesting point, as noted by the authors in to investigate if "certain transcriptomic differences [are] representative of cell state or activity, rather than cell type.
Interested? Read the full paper: "Adult mouse cortical cell taxonomy revealed by single cell transcriptomics"

Asia starts its own population sequencing project

After the success of sequencing projects like 1000G and UK10K and the recent start of the 100k Genomes Project in UK and the Precision Medicine Initiative in US, now also Asia enter the field of population scale genomics!

Indeed, a new non-profit consortium, GenomeAsia 100k, has been announced with the plan to sequence 100k individuals from populations throughout South, North, and East Asia, with the goal of creating phased reference genomes for all major Asian ethnic groups. The sequencing of 100,000 individuals will be combined with micro-biome, clinical and phenotype information to allow deeper analysis of diseased and healthy individuals.

The group is led by the Nanyang Technological University, with two private company as partners for sequencing and analysis services: Macrogen and MedGenome.

Read the official new here or the report from GenomeWeb.

System biology provides a magic wand for cell reprogramming

This is not exactly genomic, but it is based on genomic data and so fascinating that I had to report about it!

In a letter appeared recently on Nature Genetics, Rackham et al. proposed the Mogrify tool, a web-based interface that can predict the minimum set of trancription factors (TF) needed for a specific cell type reprogramming. The idea that somatic cells can be reprogrammed across different cell types has been around for a while, but a systematic assessment of the conditions needed for each conversion has never been carried out, mainly due to the amount of time and effort needed to test the various combination of TFs experimentally.

The authors took advantage of the huge amount of data produced by the FANTOM project to calculate the specific transcriptional landscape of different cell types and then developed a method that could predict which TFs should be overexpressed to move a specific cell type to another one.

With Mogrify it could be now much easier to perform reprogramming experiments, an approach with a potential great impact for regenerative medicine.

The idea behind this interesting tool is summarized in Figure 1 from the paper as you can see below

Illumina get small with new miniSeq and FireFlight

After bullying the NGS market a couple of years ago with its new large sequencing platforms able to deliver thousands of human genomes per year, now Illumina decided to further expand its offer with also small solutions.

Few days ago at JP Morgan the company revealed a new benchtop sequencer aiming at small labs and clinical application based on gene panels. The new machine, called miniSeq, can produce up to 8 Gb per run with 25M reads, costs "only" ~50k$ and promise a cost per run between $200 and $300.
With this move Illumina try to challenge Ion Torrent PGM and the Thermo Fisher good position in the area of small, rapid an cheap sequencing. The new sequencer is based on the two-color technology developed for the NextSeq and HiSeq X sequencers allowing to reduce machine cost and speed up the sequencing runs.

Look how it compares to the existing Illumina benchtop sequencers:

In its try to fill all the space in the market Illumina has also annunced an even smaller sequencer, developed under the name of "project FireFlight". The details released included a 1.2Gb output, one "colour" SBS and patterned flowcells. It also has a digital fluidics library prep module. The machine alone might cost just $15,000, with under $200 cost per run. The new machine will be based on semiconductor technology with CMOS sensor collecting light data from multiple simultaneous reactions. Project Firefly will be developed through 2016 and expect to deliver in 2017.

More details and interesting consideration have been provided on the Illumina website and other omics blogs, like CoreGenomics and OmicsOmics.