CN117789826A

CN117789826A - Gene sequencing method, device, equipment and storage medium

Info

Publication number: CN117789826A
Application number: CN202311785791.9A
Authority: CN
Inventors: 张继锋; 尚亚伟
Original assignee: Zhengzhou Sikun Biological Engineering Co ltd
Current assignee: Zhengzhou Sikun Biological Engineering Co ltd
Priority date: 2023-12-22
Filing date: 2023-12-22
Publication date: 2024-03-29

Abstract

The invention discloses a gene sequencing method, a device, equipment and a storage medium, wherein the method comprises the following steps: generating a current fluorescence image containing base information by the gene sequencer; the base sequence analysis software obtains the current fluorescence image to obtain current analysis data; in the case where the base sequence analysis software fails to output the current analysis data to a storage system, the base sequence analysis software pauses the output to the storage system. By adopting the embodiment of the invention, the current fluorescent image is analyzed by the base sequence analysis software to obtain the current analysis data; if the current analysis data cannot be output to the storage system, controlling the base sequence analysis software to suspend outputting the current analysis data, so as to avoid losing the current analysis data and causing experimental failure. The loss rate of the experiment cost is greatly reduced when the storage fault occurs, the opportunity of continuing the experiment after the storage fault is eliminated is provided, and the high-flux sequencing efficiency is improved.

Description

Gene sequencing method, device, equipment and storage medium

Technical Field

The invention relates to the field of biotechnology, in particular to a gene sequencing method, a device, equipment and a storage medium.

Background

High throughput sequencing is a DNA sequencing technology developed based on polymerase chain reaction and gene chip, which realizes sequencing while synthesis, and determines DNA sequence by capturing fluorescent molecular markers carried by newly added bases during DNA replication. In the high-throughput sequencing process, an optical sensor in the gene sequencer collects image signals of a field of view on a flow cell, converts the optical signals into digital signals, and generates a fluorescent image of a sequence. The base sequence analysis software analyzes the fluorescent image, generates analysis data of base sequence, quality value, analysis log, operation index, and the like, and directly saves and solidifies the analysis data on a memory. Therefore, the current gene sequencing is greatly influenced by software and hardware, and once a storage fault occurs, analysis data cannot be solidified on a memory, so that data loss is caused, and the experiment fails. The possible effects of experimental failure include, but are not limited to, the high cost of collecting samples again, the inability to collect gene samples again, and the high cost of sequencing boot up.

Disclosure of Invention

The invention provides a gene sequencing method, a device, equipment and a storage medium. The problem of analysis data storage failure in high-throughput sequencing is solved, and the situations of data loss and experimental failure when storage failure occurs are avoided.

According to a first aspect of the present invention there is provided a method of gene sequencing, the method comprising:

generating a current fluorescence image containing base information by the gene sequencer;

the base sequence analysis software obtains the current fluorescence image to obtain current analysis data;

in the case where the base sequence analysis software fails to output the current analysis data to a storage system, the base sequence analysis software pauses the output to the storage system.

According to a second aspect of the present invention, there is provided a gene sequencing device comprising:

a sequencing module configured to generate a current fluorescence image comprising base information by the gene sequencer;

the analysis module is configured to acquire the current fluorescence image by base sequence analysis software to obtain current analysis data;

a suspension module configured to suspend the output of the base sequence analysis software to a storage system in the event that the base sequence analysis software fails to output the current analysis data to the storage system.

According to a third aspect of the present invention, there is provided an electronic device comprising: at least one processor; and a memory communicatively coupled to the at least one processor; wherein the memory stores instructions executable by the at least one processor to cause the at least one processor to implement a method of gene sequencing according to any of the embodiments of the present invention.

According to a fourth aspect of the present invention, there is provided a computer readable storage medium, the computer instructions for causing the computer to perform a gene sequencing method according to any of the embodiments of the present invention.

It should be understood that the description in this section is not intended to identify key or critical features of the embodiments of the invention or to delineate the scope of the invention. Other features of the present invention will become apparent from the description that follows.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a schematic diagram of an application scenario of a gene sequencing method according to an embodiment of the present invention;

FIG. 2 is a flow chart of a method for sequencing a gene according to an embodiment of the present invention;

FIG. 3 is a schematic diagram of a genetic sequencing device according to an embodiment of the present invention;

FIG. 4 is a block diagram of an electronic device for implementing the gene sequencing method of an embodiment of the present invention.

Detailed Description

In order to make the present application solution better understood by those skilled in the art, the following description will be made in detail and with reference to the accompanying drawings in the embodiments of the present application, it is apparent that the described embodiments are only some embodiments of the present application, not all embodiments. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments herein without making any inventive effort, shall fall within the scope of the present application.

It should be noted that the terms "first," "second," and the like in the description and claims of the present application and the above figures are used for distinguishing between similar objects and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used may be interchanged where appropriate such that embodiments of the present application described herein may be implemented in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.

In the high throughput sequencing process, the number of field areas on the flow cell is also different for different types of gene sequencers, typically hundreds of fields or more. Where the field of view represents the minimum field of view for each sequencing fluorescent scan or photograph. According to the characteristics of high-throughput sequencing while synthesis sequencing, analysis data generated by sequencing are output to a storage system in real time, wherein the storage system comprises an internal memory, an external memory, a network memory space and other memories of the sequencer. For example, sequencer internal memory includes SSD hard disks, mechanical hard disks, and hard disk cabinets; the external memory comprises a USB mobile disk; the network storage space comprises local area network folder sharing, VPN simulation local area network, private cloud, public cloud, cloud server and the like. In response, storage system failures that may occur during gene sequencing include, but are not limited to: for internal memory, disk space is full, files are occupied and cannot be written in, disk damage, permission problems and file system errors can occur; the external memory also comprises poor USB contact, low USB interface speed, busy USB equipment and the like; for network storage space, disk space is full, files are occupied and cannot be written to, disks are damaged, rights issues, local area network failures, VPN network failures, cloud space deficiency, network failures/interruptions, rights issues, and the like can occur. Therefore, in the embodiment of the invention, under the condition that the base sequence analysis software fails to output the current analysis data to the storage system, the analysis data which is not stored at present can be well temporarily stored, and after the fault of the storage system is eliminated, the output of the analysis data is recovered, so that the smooth implementation of the experiment of gene sequencing is ensured.

Fig. 1 provides an application scenario diagram 100 of a gene sequencing method according to an embodiment of the present invention, and as shown in fig. 1, the application scenario includes a gene sequencer 110, a base sequence analysis software 120, and a storage system 130. The memory system 130 includes a sequencer internal memory 131, an external memory 132, a network memory space 133, and other memory 134. The gene sequencer 110 is a high throughput gene sequencer capable of generating a fluorescence image 101 and transmitting the fluorescence image 101 to the base sequence analysis software 120. The base sequence analysis software 120 obtains the fluorescence image 101, and performs base sequence analysis on the fluorescence image 101 according to a built-in base sequence detector to obtain the current analysis data 102, where the current analysis data 102 includes, but is not limited to, base sequence and quality values, real-time operation data, logs, and other files.

Example 1

In accordance with embodiments of the present application, a method of gene sequencing is provided, it being noted that the steps illustrated in the flowcharts of the figures may be performed in a computer system, such as a set of computer executable instructions, and, although a logical order is illustrated in the flowcharts, in some cases, the steps illustrated or described may be performed in an order other than that illustrated herein. As shown in FIG. 2, the gene sequencing method comprises the following steps: s210, S220, and S230.

S210, generating a current fluorescence image containing base information by the gene sequencer.

The high-flux gene sequencer can have hundreds of synthesis and sequencing cycles, the number of collected fluorescent images is huge, if the fluorescent images are stored, a larger storage space is occupied, based on the characteristic that high-flux sequencing is performed while synthesis is performed, the generated current fluorescent images are analyzed in real time, sequencing is performed while analysis is performed, and data obtained through analysis are solidified and stored. In the sequencing-by-synthesis process, the acquisition device in the gene sequencer scans or photographs the fluorescent signals of the same view field each time to obtain a current fluorescent image containing base information, wherein the current fluorescent image can be 1/2/4 or other fluorescent images. As an alternative embodiment, the gene sequencer of the present invention uses SIKUN2000, which incorporates control software NCS for controlling the gene sequencer to perform gene sequencing according to a preset flow.

S220, acquiring the current fluorescence image by using base sequence analysis software to obtain current analysis data.

In the gene sequencing process, the control software NCS sends the current fluorescence image containing the base information to the base sequence analysis software in a memory sharing mode. As an alternative embodiment, the base sequence analysis software of the embodiment of the present invention is self-grinding analysis software (SIKUN Sequence Analyzer, SIA), wherein the SIA performs base sequence analysis on the current fluorescence image to obtain the current analysis data, and the current analysis data comprises: base sequence, quality values, software running data, logs, and other data. And extracting base sequences and quality values according to the base detectors in the SIA, and generating software running data, logs and other data. For example, after the fluorescent image is obtained by the base sequence analysis software, the base detection is carried out on the current fluorescent image from 1 to the reading length N of the gene sequencer according to the time sequence, each time sequence is carried out once, four signals of the base sequence (A, T, C and G) are obtained, and the quality value of the base signals is obtained. Note that: in the sequencing-by-synthesis process, a group of images obtained by scanning or photographing fluorescent signals of the same field of view at a time are a time sequence fluorescent image.

S230, in the case that the base sequence analysis software fails to output the current analysis data to a storage system, the base sequence analysis software pauses to output the current analysis data to the storage system.

When the base sequence analysis software cannot output the current analysis data to the storage system, a buffer queue for file output is established, the current analysis data which is not output to the storage system is buffered in the buffer queue, and the output of the analysis data to the storage system is suspended. When the buffer queue is full, blocking the base detector to perform base detection so as to stop the base detector; when the base detector stops working, the base sequence analysis software is further blocked to analyze the current fluorescence image, and the receiving of the current fluorescence image transmitted by the gene sequencer is stopped. When the gene sequencer cannot output the current fluorescence image to the base sequence software, the control software NCS blocks the flow of the gene sequencing, and the sequencing operation of the gene sequencer is stopped. It should be noted that: the buffer queue not only buffers the current analysis data through the internal memory of the gene sequencer, but also can plan a part of storage space in other memories of the storage system as a standby storage space to buffer the current analysis data. And after the storage fault is eliminated, namely after the target storage or the network problem is solved, when the base sequence analysis software can output the current analysis data to a storage system, copying the cache data in the standby storage space to the target storage, and continuously executing the aborted gene sequencing experiment.

Optionally, the method further comprises: and under the condition that the base sequence analysis software successfully outputs the current analysis data to a storage system, the gene sequencer continues to generate a next fluorescence image containing base information until all analysis data are successfully output to the storage system.

The control software NCS controls the gene sequencer to carry out gene sequencing, generates a current fluorescence image containing base information, transmits the current fluorescence image to base sequence analysis software, and if the base sequence analysis software can normally work to obtain current analysis data and smoothly output the current analysis data to a storage system, carries out gene sequencing in real time according to a flow of sequencing and analyzing at the same time of high-throughput sequencing until all analysis data are successfully output to the storage system. For example, there are various types of data in the gene sequencing process, the data in the control software NCS is mainly a fluorescence image, and the fluorescence image can occupy 7-9TB memory space in the high-throughput sequencing process; the data in the base sequence analysis software is mainly based on base sequence, quality value and fluorescent image thumbnail, the data produced by the base sequence analysis software in the high-throughput sequencing process can occupy 300-500GB of storage space, and for example, log data, running data and other data are relatively small, and the sum is 0.5-2GB. And the fluorescent image thumbnail is an image stored after the current fluorescent image is sampled and processed and partial image data indexes are added after the base sequence analysis software acquires the current fluorescent image. Specifically, the number of fluorescence images collected in hundreds of synthesis and sequencing cycles in high-throughput sequencing is huge, so as to ensure that sequencing work is orderly and stably executed, after the storage system successfully stores the current analysis data, the built-in control software NCS of the gene sequencer is informed to release the memory space of the current fluorescence image, and the corresponding file output buffer queue is reduced, so that the requirement on the total memory is reduced, and the cost is reduced.

Optionally, the base sequence analysis software pauses outputting to the storage system, comprising: and the base sequence analysis software establishes a buffer queue according to the buffer space condition, and the buffer queue is used for buffering the current analysis data.

The buffer queue stores current analysis data to be output by the base sequence analysis software to a storage system, including but not limited to base sequence and quality values, logs, running data, fluorescence image thumbnails, and other data. Each data type generally has an independent cache queue, and the cache queues can be shared, so that the cache queues are used for determining the reasonable cache space size by clear programs running in computer equipment built in the gene sequencer and the situations of the appearance phase and other phase memory use of the peak period of the memory requirements of all programs. It should be noted that if there are separate cache queues for different data types, the total space occupied by the different cache queues should be comprehensively counted, so as to ensure that the total memory space does not exceed the maximum memory value of the computer device; for example, in addition to the buffer space of the statistical base sequence analysis software itself, the buffer space size used by the control software NCS itself, in particular, the buffer space for storing the fluorescence image should be considered.

Further, the base sequence analysis software pauses output to the storage system, comprising: and under the condition that the buffer space is full, the base sequence analysis software at least executes one of the operations of blocking the gene sequencer from generating the current fluorescence image and blocking the base sequence analysis software from acquiring the current fluorescence image.

It can be understood that under the condition that the buffer space is full, the buffer queue is not used, so that the data generation is directly blocked, and more analysis data is avoided being produced. As an alternative embodiment, the operation of the base detector is suspended, the base sequence analysis software SIA is suspended to acquire a new fluorescence image from the control software NCS, so that the control software NCS is used by itself to store the current fluorescence image with a full buffer queue, and further blocks the control software NCS; the generation of new fluorescence images is suspended, thereby blocking the operation of the gene sequencer. Alternatively, the current fluorescent image is directly blocked from being transmitted, and then the gene sequencing is blocked. Or directly blocking the gene sequencer to generate the current fluorescence image. In summary, the role of the occlusion is to avoid producing more data and to prevent exceeding the memory maximum of the built-in computer equipment of the gene sequencer.

Optionally, the base sequence analysis software pauses outputting to the storage system, comprising: and the base sequence analysis software at least executes one of the operations of blocking the generation of the current fluorescence image by the gene sequencer and blocking the acquisition of the current fluorescence image by the base sequence analysis software.

The memory space of the computer equipment built in the high-throughput gene sequencer is 128GB, and after the control software NCS and the base sequence analysis software SIA are started, the memory occupied by other software of the gene sequencer system is added, and the memory used by the gene sequencer is 30-40GB. After sequencing starts, the peak memory is 110-120GB in the initial stage of the experiment; after the peak value, the normalized memory of the gene sequencer occupies 30-40GB. If a storage fault occurs in the peak period, the residual memory space which can be provided for the cache queue is smaller, the experiment is blocked in a very short time, and after the peak period, the usable space of the cache queue is larger because the residual memory space is slightly larger, the experiment can be continued for a period of time, and after the storage fault is eliminated, the content of the cache queue is written into the storage. Otherwise, if the caching strategy is not applicable, the experiment is blocked immediately.

Optionally, before the base sequence analysis software outputs the current analysis data to a storage system, the method further includes: the base sequence analysis software verifies the operation authority of the storage system on the current analysis data; the base sequence analysis software verifies the coincidence of the current analysis data output to the storage system with expected data.

It is noted that, before any data is output to the storage system, it is required to detect whether the data content written into the storage system is consistent with the expected data format, and detect whether the storage system has operation authority on the current analysis data, so as to prevent the writing operation of the current analysis data from being inconsistent with the expected data under unexpected storage faults, so that the content of the current analysis data is missing, and once the current analysis data including the base sequence and the quality value is missing, there is a certain probability that the downstream biological information analysis cannot be performed.

Optionally, the method further comprises: after the base sequence analysis software eliminates the failure cause of failure of outputting the current analysis data to the storage system, executing analysis operation to obtain the next analysis data; and the gene sequencer releases the memory space containing the current fluorescence image according to the information of the next analysis data, and restores the gene sequencer to generate a new fluorescence image.

After the base sequence analysis software pauses the output to the storage system, waiting for the storage failure to resolve and resume, the storage failure can be resolved by an administrator. By adopting the gene sequencing method of the embodiment of the invention, an external network server is used as a memory, a local area network is established through VPN and a gene sequencer, after the gene sequencing is started, the feasibility of the method is tested by manually disconnecting the network for 8 times, each time lasting for 1-15 minutes is different, the normal operation can be carried out after the experiment is recovered, the experimental result is complete without any loss, the FASTQ file is assembled through downstream splitting software, the verification operation of the gene sequence comparison is carried out by using BWA program, and the test is error-free.

In summary, the invention limits the total memory space of the computer device built in the gene sequencer according to the memory sharing buffer queue between the NCS and the SIA. And blocking the experiment after the memory space reaches the limit value due to the storage fault or the network fault, preventing the experiment failure caused by the memory overflow, and then continuing the unfinished experiment after the storage fault is eliminated.

As an example, at a certain time of gene sequencing, the number of sequencing-by-synthesis cycles is 318, the number of fluorescent images per sequencing cycle is 768, the size of a single fluorescent image is 39MB, and the total image size is 9.1TB. Calculating the size of the occupied storage space according to the current analysis data output by the base sequence analysis software, wherein the base sequence, the quality value and the fluorescent image thumbnail occupy the storage space of about 450 GB; the log, running data and other data occupy a total of 1.5GB of storage space. And simulating and constructing a local area network with the gene sequencer through a VPN network by the other remote servers except the gene sequencer, so that the current analysis data obtained by the base sequence analysis software are generated into a shared folder of the remote servers. In the process of outputting the current analysis data to the remote server, the remote server verifies whether the output file handle where the current analysis data is located is abnormal, whether the file has normal read-write authority or not, and verifies whether the size of the written file is consistent with the expected size or not. In case of verification pass, the current analysis data is output to the remote server as a storage system. If the output fails, the remote server fails to store the current analysis data, and a cache queue is built for the output file where the current analysis data is located. The cache queue types comprise a cache queue of the SIA program and a cache queue of the NCS program; the buffer queue of the SIA program comprises a base sequence, a quality value and a thumbnail; the buffer queue of the NCS program includes fluorescence images. The time for gene sequencing is 23 hours from the beginning to the end, the memory space of the gene sequencer is 128GB, the memory used after the beginning of sequencing is 30-40GB, and the peak memory reaches 110-120GB about 20 minutes; after 30-40 minutes, the memory usage is restored to 30-40GB. Before the peak memory, no buffer queue is needed, after the peak memory, the memory usage amount is 30-40GB in normal state, and the maximum available size of the buffer queue space of the SIA program and the NCS program is 80GB. Manually disconnecting the network connection for 8 times in the experimental process, and 1-15 minutes each time; after the network is restored, the SIA program continues to execute the base detection operation of the fluorescence image, the NCS program is informed to release the memory space of the fluorescence image, the NCS program then releases the fluorescence image, the buffer queue is gradually reduced, and the gene sequencing is restored. Therefore, the embodiment of the invention dynamically designs the total size of the shared memory space occupied by the current fluorescent image transmitted between the NCS program and the SIA program according to the total amount of the residual memory of the computer equipment in the gene sequencer. After a network failure occurs, data cannot be generated to a remote server, and since sequencing is still performed, the sum of the total memory space of the SIA program cache queue and the NCS program cache queue gradually reaches a limit value of 80GB, so that before the total memory space of the computer equipment is reached, the SIA program stops fluorescent image base detection, the NCS program cannot receive notification of fluorescent image release, and after the cache queue is full, the sequencing process is suspended. Therefore, the gene sequencing method of the invention realizes that the blocking program continues to run before the total memory space of the gene sequencer is insufficient, thereby blocking the sequencing experiment progress and avoiding producing more data.

The embodiment of the invention discloses a gene sequencing method, which comprises the following steps: generating a current fluorescence image containing base information by the gene sequencer; the base sequence analysis software obtains the current fluorescence image to obtain current analysis data; in the case where the base sequence analysis software fails to output the current analysis data to a storage system, the base sequence analysis software pauses the output to the storage system. By adopting the embodiment of the invention, the current fluorescent image is analyzed by the base sequence analysis software to obtain the current analysis data; if the current analysis data cannot be output to the storage system, controlling the base sequence analysis software to suspend outputting the current analysis data, so as to avoid losing the current analysis data and causing experimental failure. The loss rate of the experiment cost is greatly reduced when the storage fault occurs, the opportunity of continuing the experiment after the storage fault is eliminated is provided, and the high-flux sequencing efficiency is improved.

Example two

According to an embodiment of the present invention, a schematic structural diagram of a genetic sequencing device is provided, and the genetic sequencing device may perform the genetic sequencing method provided in the first embodiment. As shown in fig. 3, the apparatus includes: a sequencing module 310, an analysis module 320, and a pause module 330. Wherein:

A sequencing module 310 configured to generate a current fluorescence image comprising base information by the gene sequencer.

And the analysis module 320 is configured to obtain the current fluorescence image by using base sequence analysis software to obtain current analysis data.

A suspension module 330 configured to suspend the output of the base sequence analysis software to the storage system in the event that the base sequence analysis software fails to output the current analysis data to the storage system.

Optionally, the apparatus further includes: and under the condition that the base sequence analysis software successfully outputs the current analysis data to a storage system, the gene sequencer continues to generate a next fluorescence image containing base information until all analysis data are successfully output to the storage system.

Optionally, the suspension module includes: and the base sequence analysis software establishes a buffer queue according to the buffer space condition, and the buffer queue is used for buffering the current analysis data.

Further, the pause module includes: and under the condition that the buffer space is full, the base sequence analysis software at least executes one of the operations of blocking the gene sequencer from generating the current fluorescence image and blocking the base sequence analysis software from acquiring the current fluorescence image.

Optionally, the suspension module further includes: and the base sequence analysis software at least executes one of the operations of blocking the generation of the current fluorescence image by the gene sequencer and blocking the acquisition of the current fluorescence image by the base sequence analysis software.

Optionally, the apparatus further includes: after the base sequence analysis software eliminates the failure cause of failure of outputting the current analysis data to the storage system, executing analysis operation to obtain the next analysis data; and the gene sequencer releases the memory space containing the current fluorescence image according to the information of the next analysis data, and restores the gene sequencer to generate a new fluorescence image.

The embodiment of the invention discloses a gene sequencing device, which comprises: a sequencing module configured to generate a current fluorescence image comprising base information by the gene sequencer; the analysis module is configured to acquire the current fluorescence image by base sequence analysis software to obtain current analysis data; a suspension module configured to suspend the output of the base sequence analysis software to a storage system in the event that the base sequence analysis software fails to output the current analysis data to the storage system. By adopting the embodiment of the invention, the current fluorescent image is analyzed by the base sequence analysis software to obtain the current analysis data; if the current analysis data cannot be output to the storage system, controlling the base sequence analysis software to suspend outputting the current analysis data, so as to avoid losing the current analysis data and causing experimental failure. The loss rate of the experiment cost is greatly reduced when the storage fault occurs, the opportunity of continuing the experiment after the storage fault is eliminated is provided, and the high-flux sequencing efficiency is improved.

Example III

Referring now to FIG. 4, a block diagram of an electronic device 400 suitable for use in implementing embodiments of the present invention is shown. Electronic devices are intended to represent various forms of digital computers, such as laptops, desktops, workstations, personal digital assistants, servers, blade servers, mainframes, and other appropriate computers. The electronic device may also represent various forms of mobile devices, such as personal digital processing, cellular telephones, smartphones, wearable devices, and other similar computing devices. The components shown herein, their connections and relationships, and their functions, are meant to be exemplary only, and are not meant to limit implementations of the inventions described and/or claimed herein.

As shown in fig. 4, the electronic device 400 may include a processing means 410 that may perform various suitable actions and processes according to a program stored in a Read Only Memory (ROM) 420 or a program loaded from a storage means 480 into a Random Access Memory (RAM) 430. The processing device 410 may be a variety of general purpose and/or special purpose processing components having processing and computing capabilities. Some examples of processing device 410 include, but are not limited to, a Central Processing Unit (CPU), a Graphics Processing Unit (GPU), various specialized Artificial Intelligence (AI) computing chips, various computing units running machine learning model algorithms, a Digital Signal Processor (DSP), and any suitable processor, controller, microcontroller, etc. The processing device 410 performs the various methods and processes described above.

In the RAM 430, various programs and data required for the operation of the electronic device 400 are also stored. The processing device 410, ROM 420, and RAM 430 are connected to each other by a bus 440. An input/output (I/O) interface 450 is also connected to bus 440.

In general, the following devices may be connected to the I/O interface 450: input devices 460 including, for example, a touch screen, touchpad, keyboard, mouse, camera, microphone, accelerometer, gyroscope, and the like; an output device 470 including, for example, a Liquid Crystal Display (LCD), a speaker, a vibrator, etc.; storage 480 including, for example, magnetic tape, hard disk, etc.; and communication device 490. The communication means 490 may allow the electronic device 400 to communicate wirelessly or by wire with other devices to exchange data. While fig. 4 shows an electronic device 400 having various means, it is to be understood that not all of the illustrated means are required to be implemented or provided. More or fewer devices may be implemented or provided instead.

In particular, according to embodiments of the present invention, the processes described above with reference to flowcharts may be implemented as computer software programs. For example, embodiments of the present invention include a computer program product comprising a computer program embodied on a non-transitory computer readable medium, the computer program comprising program code for performing the method shown in the flow chart. In such an embodiment, the computer program may be downloaded and installed from a network via communications device 490, or installed from storage 480, or installed from ROM 420. The above-described functions defined in the method of the embodiment of the present invention are performed when the computer program is executed by the processing means 410. Alternatively, in other embodiments, the processing device 410 may be configured to perform the method by any other suitable means (e.g., by means of firmware): generating a current fluorescence image containing base information by the gene sequencer; the base sequence analysis software obtains the current fluorescence image to obtain current analysis data; in the case where the base sequence analysis software fails to output the current analysis data to a storage system, the base sequence analysis software pauses the output to the storage system.

Example IV

The computer readable medium of the present invention described above may be a computer readable signal medium or a computer readable storage medium or any combination of the two. The computer readable storage medium can be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or a combination of any of the foregoing. More specific examples of the computer-readable storage medium may include, but are not limited to: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a Random Access Memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device. In the present invention, however, the computer-readable signal medium may include a data signal propagated in baseband or as part of a carrier wave, with the computer-readable program code embodied therein. Such a propagated data signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination of the foregoing. A computer readable signal medium may also be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device. Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to: electrical wires, fiber optic cables, RF (radio frequency), and the like, or any suitable combination of the foregoing.

In some implementations, the clients, servers may communicate using any currently known or future developed network protocol, such as HTTP (HyperText Transfer Protocol ), and may be interconnected with any form or medium of digital data communication (e.g., a communication network). Examples of communication networks include a local area network ("LAN"), a wide area network ("WAN"), the internet (e.g., the internet), and peer-to-peer networks (e.g., ad hoc peer-to-peer networks), as well as any currently known or future developed networks.

The computer readable medium may be contained in the electronic device; or may exist alone without being incorporated into the electronic device.

The computer readable medium carries one or more programs which, when executed by the electronic device, cause the electronic device to: generating a current fluorescence image containing base information by the gene sequencer; the base sequence analysis software obtains the current fluorescence image to obtain current analysis data; in the case where the base sequence analysis software fails to output the current analysis data to a storage system, the base sequence analysis software pauses the output to the storage system.

Computer program code for carrying out operations of the present invention may be written in one or more programming languages, including, but not limited to, an object oriented programming language such as Java, smalltalk, C ++ and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the case of a remote computer, the remote computer may be connected to the user's computer through any kind of network, including a Local Area Network (LAN) or a Wide Area Network (WAN), or may be connected to an external computer (for example, through the Internet using an Internet service provider).

The flowcharts and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems which perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.

The modules involved in the embodiments of the present invention may be implemented in software or in hardware. The name of a module does not in some cases define the module itself.

The functions described above herein may be performed, at least in part, by one or more hardware logic components. For example, without limitation, exemplary types of hardware logic components that may be used include: digital electronic circuitry, integrated circuitry, field Programmable Gate Arrays (FPGAs), application Specific Integrated Circuits (ASICs), application Specific Standard Products (ASSPs), systems On Chip (SOCs), complex Programmable Logic Devices (CPLDs), computer hardware, firmware, software, and/or combinations thereof, and the like.

Program code for carrying out methods of the present invention may be written in any combination of one or more programming languages. These program code may be provided to a processor or controller of a general purpose computer, special purpose computer, or other programmable data processing apparatus such that the program code, when executed by the processor or controller, causes the functions/operations specified in the flowchart and/or block diagram to be implemented. The program code may execute entirely on the machine, partly on the machine, as a stand-alone software package, partly on the machine and partly on a remote machine or entirely on the remote machine or server.

In the context of the present invention, a machine-readable medium may be a tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device. The machine-readable medium may be a machine-readable signal medium or a machine-readable storage medium. The machine-readable medium may include, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples of a machine-readable storage medium would include an electrical connection based on one or more wires, a portable computer diskette, a hard disk, a Random Access Memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing.

To provide for interaction with a user, the systems and techniques described here can be implemented on a computer having: a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying information to a user; and a keyboard and pointing device (e.g., a mouse or trackball) by which a user can provide input to the computer. Other kinds of devices may also be used to provide for interaction with a user; for example, feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user may be received in any form, including acoustic input, speech input, or tactile input.

The systems and techniques described here can be implemented in a computing system that includes a background component (e.g., as a data server), or that includes a middleware component (e.g., an application server), or that includes a front-end component (e.g., a user computer having a graphical user interface or a web browser through which a user can interact with an implementation of the systems and techniques described here), or any combination of such background, middleware, or front-end components. The components of the system can be interconnected by any form or medium of digital data communication (e.g., a communication network). Examples of communication networks include: local Area Networks (LANs), wide Area Networks (WANs), blockchain networks, and the internet.

The computer system may include a client and a server. The client and server are typically remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. The server can be a cloud server, also called a cloud computing server or a cloud host, and is a host product in a cloud computing service system, so that the defects of high management difficulty and weak service expansibility in the traditional physical hosts and VPS service are overcome. The server may also be a server of a distributed system or a server that incorporates a blockchain.

Artificial intelligence is the discipline of studying the process of making a computer mimic certain mental processes and intelligent behaviors (e.g., learning, reasoning, thinking, planning, etc.) of a person, both hardware-level and software-level techniques. Artificial intelligence hardware technologies generally include technologies such as sensors, dedicated artificial intelligence chips, cloud computing, distributed storage, big data processing, and the like; the artificial intelligent software technology mainly comprises a computer vision technology, a voice recognition technology, a natural language processing technology, a machine learning/deep learning technology, a big data processing technology, a knowledge graph technology and the like.

Cloud computing (cloud computing) refers to a technical system that a shared physical or virtual resource pool which is elastically extensible is accessed through a network, resources can comprise servers, operating systems, networks, software, applications, storage devices and the like, and resources can be deployed and managed in an on-demand and self-service mode. Through cloud computing technology, high-efficiency and powerful data processing capability can be provided for technical application such as artificial intelligence and blockchain, and model training.

It should be appreciated that various forms of the flows shown above may be used to reorder, add, or delete steps. For example, the steps described in the present invention may be performed in parallel, sequentially, or in a different order, so long as the desired result of the technical solution provided by the present invention is achieved, and the present invention is not limited herein.

The above embodiments do not limit the scope of the present invention. It will be apparent to those skilled in the art that various modifications, combinations, sub-combinations and alternatives are possible, depending on design requirements and other factors. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of the present invention.

Claims

1. A method of gene sequencing, the method comprising:

2. The method according to claim 1, wherein the method further comprises:

and under the condition that the base sequence analysis software successfully outputs the current analysis data to a storage system, the gene sequencer continues to generate a next fluorescence image containing base information until all analysis data are successfully output to the storage system.

3. The method of claim 1, wherein the base sequence analysis software pauses output to the storage system, comprising:

and the base sequence analysis software establishes a buffer queue according to the buffer space condition, and the buffer queue is used for buffering the current analysis data.

4. The method of claim 3, wherein the base sequence analysis software pauses output to the storage system, comprising:

and under the condition that the buffer space is full, the base sequence analysis software at least executes one of the operations of blocking the gene sequencer from generating the current fluorescence image and blocking the base sequence analysis software from acquiring the current fluorescence image.

5. The method of claim 1, wherein the base sequence analysis software pauses output to the storage system, comprising:

and the base sequence analysis software at least executes one of the operations of blocking the generation of the current fluorescence image by the gene sequencer and blocking the acquisition of the current fluorescence image by the base sequence analysis software.

6. The method according to claim 1, further comprising, before the base sequence analysis software outputs the current analysis data to a storage system:

The base sequence analysis software verifies the operation authority of the storage system on the current analysis data;

the base sequence analysis software verifies the coincidence of the current analysis data output to the storage system with expected data.

7. The method according to claim 1, wherein the method further comprises:

after the base sequence analysis software eliminates the failure cause of failure of outputting the current analysis data to the storage system, executing analysis operation to obtain the next analysis data;

and the gene sequencer releases the memory space containing the current fluorescence image according to the information of the next analysis data, and restores the gene sequencer to generate a new fluorescence image.

8. A genetic sequencing device, the device comprising:

9. An electronic device, comprising:

at least one processor; and

a memory communicatively coupled to the at least one processor; wherein,

the memory stores instructions executable by the at least one processor to cause the at least one processor to implement the method of any one of claims 1-7.

10. A computer readable storage medium storing computer instructions, wherein the computer instructions are for causing the computer to perform the method according to any one of claims 1-7.