FamSeq: A Variant Calling Program for Family-Based Sequencing Data Using Graphics Processing Units

<div><p>Various algorithms have been developed for variant calling using next-generation sequencing data, and various methods have been applied to reduce the associated false positive and false negative rates. Few variant calling programs, however, utilize the pedigree information when the family-based sequencing data are available. Here, we present a program, FamSeq, which reduces both false positive and false negative rates by incorporating the pedigree information from the Mendelian genetic model into variant calling. To accommodate variations in data complexity, FamSeq consists of four distinct implementations of the Mendelian genetic model: the Bayesian network algorithm, a graphics processing unit version of the Bayesian network algorithm, the Elston-Stewart algorithm and the Markov chain Monte Carlo algorithm. To make the software efficient and applicable to large families, we parallelized the Bayesian network algorithm that copes with pedigrees with inbreeding loops without losing calculation precision on an NVIDIA graphics processing unit. In order to compare the difference in the four methods, we applied FamSeq to pedigree sequencing data with family sizes that varied from 7 to 12. When there is no inbreeding loop in the pedigree, the Elston-Stewart algorithm gives analytical results in a short time. If there are inbreeding loops in the pedigree, we recommend the Bayesian network method, which provides exact answers. To improve the computing speed of the Bayesian network method, we parallelized the computation on a graphics processing unit. This allowed the Bayesian network method to process the whole genome sequencing data of a family of 12 individuals within two days, which was a 10-fold time reduction compared to the time required for this computation on a central processing unit.</p></div

Workflow of FamSeq.

<p>We use a pedigree file and a file that includes the likelihood () as the input to estimate the posterior probability () for each variant genotype. (E-S: Elston-Stewart algorithm; BN: Bayesian network method; BN-GPU: The computer needs a GPU card installed to run the GPU version of the Bayesian network method; MCMC: Markov chain Monte Carlo method; VCF: variant call format.)</p

Illustration of input files.

<p>A.) Pedigree structure. B.) Pedigree structure file storing the pedigree structure shown in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003880#pcbi-1003880-g002" target="_blank">Fig. 2A</a>. From the left-most column to the right-most column, the data are ID, mID (mother ID), fID (father ID), gender and sample name. C.) Part of VCF file. From the VCF file, we can find that the genome of the grandfather (G-Father) was not sequenced. We add his information to the pedigree structure file to avoid ambiguity. For example, if we include only one parent of two siblings in the pedigree structure file, it will be unclear whether they are full or half siblings. The sample name in the pedigree structure file should be the same as the sample name in the VCF file. When the actual genome was not sequenced, we set the corresponding sample name as NA in the pedigree structure file.</p

Illustration of GPU parallel computing in FamSeq.

<p>The program can be divided into two parts: a serial part and a parallel part. The serial part is processed in a CPU and the parallel part is processed in a GPU. The program: 1. Prepare the data for parallel computing in a CPU; 2. Copy the data from CPU memory to GPU memory; 3. Parallelize the 3ⁿ jobs computing in the GPU, where n is the pedigree size; 4. Copy the results from GPU memory to CPU memory; and 5. Summarize the results in the CPU.</p

The total time (in seconds) needed for computation using FamSeq at one million positions.

<p>PU: processing unit; E-S: Elston-Stewart algorithm; MCMC: Markov chain Monte Carlo algorithm; BN: Bayesian network algorithm; N: No, inbreeding loops are not considered; Y: Yes, inbreeding loops are considered.</p>a<p>We called only 100,000 variants due to excessive running time for the MCMC algorithm. The time shown here is 10× the time required to call 100,000 variants.</p>b<p>The time in parentheses is the GPU computing time.</p><p>The total time (in seconds) needed for computation using FamSeq at one million positions.</p

Supplemental Material - Mistuning identification and model updating of a blisk with piezoelectric excitation components

Supplemental Material for Mistuning identification and model updating of a blisk with piezoelectric excitation components by Anlue Li, Yu Fan, Hui Wang, Yaguang Wu and Lin Li in Journal of Vibration and Control.</p

Additional file 1 of Determinants and outcomes of health-promoting lifestyle among people with schizophrenia

Supplementary Material

Petrogenesis and metallogenic implications for the Machang, Huangdaoshan, and Tuncang plutons in eastern Anhui: an integrated age, petrologic, and geochemical study

<p>The Tuncang–Chuzhou–Machang area (eastern Anhui province) is geologically located in the intersection between the Yangtze block and the Qinling–Dabie orogenic belt. Many Mesozoic plutons outcrop in this district that are Cu–Au prospective but inadequately studied. We report new LA-ICP-MS zircon U–Pb ages, petrologic, and whole rock geochemical data for three representative plutons at Machang, Huangdaoshan, and Tuncang. New dating results suggest that all the Machang (129.3 ± 1.6 Ma), Huangdaoshan (129 ± 1.7 Ma), and Tuncang (130.8 ± 1.9 Ma) plutons were emplaced in the Early Cretaceous, slightly older than other plutons in neighbourhood of the Zhangbaling uplift. The three plutons contain typical low-Mg adakitic affinities, in which the rocks contain SiO₂ >56%, Al₂O₃ ≥15%, Mg# <53, elevated Sr, Ba, Cr, Ni, Sr/Y, and La/Yb, low Y and Yb and no discernible Eu anomaly. Their petrogenesis may have been related to the delamination and partial melting of the lower crust, which is different from the Chuzhou pluton, which was interpreted to have formed by partial melting of the subducted slabs. We suggest that this petrogenetic difference may explain why the pluton at Chuzhou is Cu–Au fertile, whereas those at Machang, Huangdaoshan, and Tuncang are largely barren. It is proposed that adakitic plutons formed by partial melting of the subducted slabs have high metallogenetic potentiality in the area.</p

Additional file 1 of Pretreatment prostate-specific antigen density as a predictor of biochemical recurrence in patients with prostate cancer: a meta-analysis

Supplementary Material

Comparison of different dispersed phase^a.

a<p>Data are averages of three independent experiments with standard deviations.</p