Re-identification of genomic data using long range familial searches, bioRxiv, 2018-06-18

AbstractConsumer genomics databases reached the scale of millions of individuals. Recently, law enforcement investigators have started to exploit some of these databases to find distant familial relatives, which can lead to a complete re-identification. Here, we leveraged genomic data of 600,000 individuals tested with consumer genomics to investigate the power of such long-range familial searches. We project that half of the searches with European-descent individuals will result with a third cousin or closer match and will provide a search space small enough to permit re-identification using common demographic identifiers. Moreover, in the near future, virtually any European-descent US person could be implicated by this technique. We propose a potential mitigation strategy based on cryptographic signature that can resolve the issue and discuss policy implications to human subject research.

biorxiv genomics 500+-users 2018

Thousands of large-scale RNA sequencing experiments yield a comprehensive new human gene list and reveal extensive transcriptional noise, bioRxiv, 2018-05-28

AbstractWe assembled the sequences from 9,795 RNA sequencing experiments, collected from 31 human tissues and hundreds of subjects as part of the GTEx project, to create a new, comprehensive catalog of human genes and transcripts. The new human gene database contains 43,162 genes, of which 21,306 are protein-coding and 21,856 are noncoding, and a total of 323,824 transcripts, for an average of 7.5 transcripts per gene. Our expanded gene list includes 4,998 novel genes (1,178 coding and 3,819 noncoding) and 97,511 novel splice variants of protein-coding genes as compared to the most recent human gene catalogs. We detected over 30 million additional transcripts at more than 650,000 sites, nearly all of which are likely to be nonfunctional, revealing a heretofore unappreciated amount of transcriptional noise in human cells.

biorxiv genomics 500+-users 2018

Fast animal pose estimation using deep neural networks, bioRxiv, 2018-05-25

AbstractRecent work quantifying postural dynamics has attempted to define the repertoire of behaviors performed by an animal. However, a major drawback to these techniques has been their reliance on dimensionality reduction of images which destroys information about which parts of the body are used in each behavior. To address this issue, we introduce a deep learning-based method for pose estimation, LEAP (LEAP Estimates Animal Pose). LEAP automatically predicts the positions of animal body parts using a deep convolutional neural network with as little as 10 frames of labeled data for training. This framework consists of a graphical interface for interactive labeling of body parts and software for training the network and fast prediction on new data (1 hr to train, 185 Hz predictions). We validate LEAP using videos of freely behaving fruit flies (Drosophila melanogaster) and track 32 distinct points on the body to fully describe the pose of the head, body, wings, and legs with an error rate of <3% of the animal’s body length. We recapitulate a number of reported findings on insect gait dynamics and show LEAP’s applicability as the first step in unsupervised behavioral classification. Finally, we extend the method to more challenging imaging situations (pairs of flies moving on a mesh-like background) and movies from freely moving mice (Mus musculus) where we track the full conformation of the head, body, and limbs.

biorxiv animal-behavior-and-cognition 500+-users 2018

The Genomic Formation of South and Central Asia, bioRxiv, 2018-03-31

AbstractThe genetic formation of Central and South Asian populations has been unclear because of an absence of ancient DNA. To address this gap, we generated genome-wide data from 362 ancient individuals, including the first from eastern Iran, Turan (Uzbekistan, Turkmenistan, and Tajikistan), Bronze Age Kazakhstan, and South Asia. Our data reveal a complex set of genetic sources that ultimately combined to form the ancestry of South Asians today. We document a southward spread of genetic ancestry from the Eurasian Steppe, correlating with the archaeologically known expansion of pastoralist sites from the Steppe to Turan in the Middle Bronze Age (2300-1500 BCE). These Steppe communities mixed genetically with peoples of the Bactria Margiana Archaeological Complex (BMAC) whom they encountered in Turan (primarily descendants of earlier agriculturalists of Iran), but there is no evidence that the main BMAC population contributed genetically to later South Asians. Instead, Steppe communities integrated farther south throughout the 2nd millennium BCE, and we show that they mixed with a more southern population that we document at multiple sites as outlier individuals exhibiting a distinctive mixture of ancestry related to Iranian agriculturalists and South Asian hunter-gathers. We call this group Indus Periphery because they were found at sites in cultural contact with the Indus Valley Civilization (IVC) and along its northern fringe, and also because they were genetically similar to post-IVC groups in the Swat Valley of Pakistan. By co-analyzing ancient DNA and genomic data from diverse present-day South Asians, we show that Indus Periphery-related people are the single most important source of ancestry in South Asia—consistent with the idea that the Indus Periphery individuals are providing us with the first direct look at the ancestry of peoples of the IVC—and we develop a model for the formation of present-day South Asians in terms of the temporally and geographically proximate sources of Indus Periphery-related, Steppe, and local South Asian hunter-gatherer-related ancestry. Our results show how ancestry from the Steppe genetically linked Europe and South Asia in the Bronze Age, and identifies the populations that almost certainly were responsible for spreading Indo-European languages across much of Eurasia.One Sentence SummaryGenome wide ancient DNA from 357 individuals from Central and South Asia sheds new light on the spread of Indo-European languages and parallels between the genetic history of two sub-continents, Europe and South Asia.

biorxiv genomics 500+-users 2018

A comprehensive toolkit to enable MinION sequencing in any laboratory, bioRxiv, 2018-03-27

AbstractLong-read sequencing technologies are transforming our ability to assemble highly complex genomes. Realising their full potential relies crucially on extracting high quality, high molecular weight (HMW) DNA from the organisms of interest. This is especially the case for the portable MinION sequencer which potentiates all laboratories to undertake their own genome sequencing projects, due to its low entry cost and minimal spatial footprint. One challenge of the MinION is that each group has to independently establish effective protocols for using the instrument, which can be time consuming and costly. Here we present a workflow and protocols that enabled us to establish MinION sequencing in our own laboratories, based on optimising DNA extractions from a challenging plant tissue as a case study. Following the workflow illustrated we were able to reliably and repeatedly obtain > 8.5 Gb of long read sequencing data with a mean read length of 13 kb and an N50 of 26 kb. Our protocols are open-source and can be performed in any laboratory without special equipment. We also illustrate some more elaborate workflows which can increase mean and average read lengths if this is desired. We envision that our workflow for establishing MinION sequencing, including the illustration of potential pitfalls, will be useful to others who plan to establish long-read sequencing in their own laboratories.

biorxiv genomics 500+-users 2018

Patterns of genetic differentiation and the footprints of historical migrations in the Iberian Peninsula, bioRxiv, 2018-03-13

Genetic differences within or between human populations (population structure) has been studied using a variety of approaches over many years. Recently there has been an increasing focus on studying genetic differentiation at fine geographic scales, such as within countries. Identifying such structure allows the study of recent population history, and identifies the potential for confounding in association studies, particularly when testing rare, often recently arisen variants. The Iberian Peninsula is linguistically diverse, has a complex demographic history, and is unique among European regions in having a centuries-long period of Muslim rule. Previous genetic studies of Spain have examined either a small fraction of the genome or only a few Spanish regions. Thus, the overall pattern of fine-scale population structure within Spain remains uncharacterised. Here we analyse genome-wide genotyping array data for 1,413 Spanish individuals sampled from all regions of Spain. We identify extensive fine-scale structure, down to unprecedented scales, smaller than 10 Km in some places. We observe a major axis of genetic differentiation that runs from east to west of the peninsula. In contrast, we observe remarkable genetic similarity in the north-south direction, and evidence of historical north-south population movement. Finally, without making particular prior assumptions about source populations, we show that modern Spanish people have regionally varying fractions of ancestry from a group most similar to modern north Moroccans. The north African ancestry results from an admixture event, which we date to 860 - 1120 CE, corresponding to the early half of Muslim rule. Our results indicate that it is possible to discern clear genetic impacts of the Muslim conquest and population movements associated with the subsequent Reconquista.

biorxiv genomics 500+-users 2018