Time to Retire HeLa?
A TV movie produced by and starring American culture mogul Oprah Winfrey is about to hit screens which dramatizes Rebecca Skloot'sThe Immortal Life of Henrietta Lacks.  If you haven't read this remarkable book, you really should.  It should certainly be required reading for anyone entering biomedical fields.  That's not to claim it is perfect; one of Lacks' sons has objected to the way his family is portrayed.  But it is a searing human story of how the most famous cell line in the world came to be.  Even if you excuse some of the injustices done as compatible with then contemporary ethical standards, ...
Source: Omics! Omics! - April 20, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Alexandria Jumps Into Shuttle Business
A restaurant I frequented during my grad school days had a map on the wall showing Boston area transit routes from roughly the 1940s.  Remarkably, most of those streetcar routes are found largely unchanged in the MBTA's current bus routes.  Yes, routes have been altered to account for expansion of the Red Line and shifting of the Orange Line, but most of the routes are little changed and very, very few new ones have been added.  Some of that reflects the canalization of routes by the street patterns; there are only so many large str eets suitable for buses and Somerville's hills and the various rivers impose fur...
Source: Omics! Omics! - April 13, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

10x Launches Mass T-Cell Receptor Decoding
Adaptive immunity is an endlessly fascinating topic which I have not explored very deeply, which is particularly unfortunate given the many parallels to computing.  Combinatorial logic is used to construct a vast array of possible antigen readers, expression logic ensures that only one such reader is expressed in a given cell and hypermutation and evolution are used to optimize these readers to match specific antigens.  All this not only creates weapons to d eploy against foreign invaders, but also a memory which effectively records an individual's history of environmental exposures.  Just before I started writing t...
Source: Omics! Omics! - April 10, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

SageHLS: Automated uHMW DNA Preparation
Advances in optical mapping, linked reads, PacBio and nanopore sequencing are enabling generatinghighly contiguous large genome sequences routinely and inexpensively.  However, this in turn is creating intense demand for efficiently and reliably preparing ultra-high molecular weight (uHMW) DNA.  By this term,  I mean DNA approaching or exceeding a megabase in size.  Methods for preparing HMW and uHMW DNA tend to be very old-school, reaching back at least back to the 1970s, 80s and 90s for approaches used in the early days.  Phenol-chloroform preps with the DNA spooled out onto a glass hook or rod are one popular appro...
Source: Omics! Omics! - April 4, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Chromosome-Scale Scaffolds And The State of Genome Assembly
A new paper on using Hi-C sequencing appeared in Science recently, demonstrating the generation of chromosome-length scaffolds for human as well as several insect genomes.  The authors even provide a cost model, proposing that by processing multiple genomes in parallel the sequencing reagent cost (but not labor) of this approach should be about $10K per human genome. In the case of the insect genomes, the paper enables a look at chromosome evolution which is simply i mpossible with lower resolution.  These findings resonate with a number of pieces I've written over the years, but particularly withmy recent criticism ...
Source: Omics! Omics! - March 30, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Differential Mammalian Toxicity: Why Do Some Human Foods Kill Dogs?
I've been contemplating this post for a while, but it can be seen as another angle onmy recent post on the challenges of drug discovery, so it finally left the mental queue.  We often use other mammalian species in drug development to predict human toxicity.  We know animals aren't the same as people, but lacking a better alternative that's what we do.  Now, as regular readers know I keep company with a dog, and that sometimes has me wondering: how well do we understand the cases of things we can eat but which are dangerous for our canines?Read more » (Source: Omics! Omics!)
Source: Omics! Omics! - March 27, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Targets: Drugability Revisited
My correspondent  @datarade shot a tweet my way on his quest to understand drug discovery. He does this despite the fact I've promised posts on previous tweets that are submerged in my mental queue.  But the best part of teaching is forcing yourself to rethink what you think you know, so I'm going to actually take this one on in the space of"what is a target, how do we pick them and how do we drug them".  Which I've found to be enlightening and frustrating.  It's a messy space because so much is empirical, and I keep devising and then discarding taxonomies and explanatory approaches because th...
Source: Omics! Omics! - March 25, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Obviousness: Rarely Obvious
Pacific Biosciences has made new thrusts in theirongoing intellectual property action against Oxford Nanopore, adding two recently issued patents to the fray.  Oxford has publicly brushed these off as"another pore excuse for a lawsuit", but certainly the battle is not over.  One of these patents, 9,542,527"Compositions and methods for nucleic acid sequencing", appears to concern using hairpin linkages to read both strands, much likethe 9,404,146"Compositions and methods for nucleic acid sequencing"  patent that PacBio led with.  Since Oxfordhas announced they will abandon their"2D&...
Source: Omics! Omics! - March 21, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

plexWell: Illumina Libraries by the Plateload
The advent of so-called next generation sequencers, particularly those from Illumina, have brought the price of sequence data down dramatically.  However, there is a catch: the cost of preparing DNA to go into the sequencer, the process known as library preparation, has glided downwards on a much shallower trajectory.  This means that for projects wishing to sequence very large numbers of small genomes or large constructs the cost of libra ry preparation can be similar to or even exceed the cost of data generation.  A small company north of Boston calledseqWell Inc™ has a new approach to Illumina library generation w...
Source: Omics! Omics! - March 19, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

ONT Updates: GridION X5, PromethION, 1D^2, Scrappie, FPGAs and More
Clive Brown gave a webcast today with updates on a number of Oxford Nanopore topics, but clearly the flagship announcement was a new instrument, GridION X5.  Due to the raging snowstorm in the Boston area I was home with my teammate and we've been doggedly going through the tweets (now storified) and my notes (plusDavid Eccles' nice set) to retrieve the juiciest bones therein.Blog team member intently watching@Clive_G_Brown webcast - now must confer& write-up impressionspic.twitter.com/jPGpw1w0lg— Keith Robison (@OmicsOmicsBlog)March 14, 2017Read more » (Source: Omics! Omics!)
Source: Omics! Omics! - March 13, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

MinION Leviathan Reads: An Update
Last week I posted a piece on some amazing new nanopore data, only to be red-faced to discover the next morning that I had misread the axes.  So I re-posted the piece with the offending data and subsequent analysis in strike-thru font.  After I did that, I was informed that the same dataset actually did have leviathan rea ds, bigger than my misinterpretation.Read more » (Source: Omics! Omics!)
Source: Omics! Omics! - March 7, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Catching Up On Oxford Nanopore News: More, Better, Meth & Huge
Oxford Nanopore and its collaborators have shown at least three interesting advances in the last few months which I haven't yet covered; the most astounding of which was announced this week.  I'll take these three in an order which works logically for me, though it isn't strictly chronological plus I'll touch on some parts of their platform which have not made advances which were perhaps expected.Read more » (Source: Omics! Omics!)
Source: Omics! Omics! - March 1, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Earth BioGenome Project: Ill-Conceived Megaproject Du Jour
There's been a bit of buzz recently about an unfunded proposal to ultimately sequence every living species on Earth, warming up by sequencing every eukaryotic species, with a targeted cost of $4.8B.  It pains me a bit to write this, but I'm with those who think this is not a wise way to spend money and certainly not likely to work for anywhere near that budget.Read more » (Source: Omics! Omics!)
Source: Omics! Omics! - February 27, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

#AGBT17 Tweet Archive is Up!
I've used my scheme for collecting and organizing tweets to capture most of the feed from this week's AGBT17 conference.  I still need to pore over these in detail, so I won't try to distill out much thoughts (other than single-cell sequencing is clearly in exponential growth phase!).Read more » (Source: Omics! Omics!)
Source: Omics! Omics! - February 16, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs

Bagging Novel Enzymes Via Mass Spec Metabolomics
Obtaining a complete genome sequence for a bacterium or archean is essentially a solved problem, if you can culture the bug.  Grow up biomass, purify the DNA and then use PacBio alone or a combination of long reads (PacBio or Oxford Nanopore) and short reads.  These should yield a closed genome with a very low error rate.  A few bugs spit at you by repeated failing PacBio sequencing or having some monster prophage or o ther repeat that is longer than the read lengths, but these are very rare.  With advances in metagenomics techniques, the solving of uncultured genomes is becoming increasingly easy and many of these rem...
Source: Omics! Omics! - February 12, 2017 Category: Bioinformatics Authors: Keith Robison Source Type: blogs