Python 获取 NCBI 基因名 SSL 证书出现异常？

源自于前几天对一批转录本的批量化操作的一些记录。

即想要通过 Python 在线获取某个转录本对应的基因 Symbol 时，发现出现 SSL 无法获取本地证书：unable to get local issuer certificate (_ssl.c:1056)！

>>> from Bio import SeqIO
>>> from Bio import Entrez
>>> Entrez.email = "A.N.Other@example.com"
>>> records = SeqIO.parse(Entrez.efetch(id='NM_001009537.4', db="nucleotide", rettype="gb", retmode="text"), "gb")
Traceback (most recent call last):
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 1317, in do_open
    encode_chunked=req.has_header('Transfer-encoding'))
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/http/client.py", line 1229, in request
    self._send_request(method, url, body, headers, encode_chunked)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/http/client.py", line 1275, in _send_request
    self.endheaders(body, encode_chunked=encode_chunked)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/http/client.py", line 1224, in endheaders
    self._send_output(message_body, encode_chunked=encode_chunked)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/http/client.py", line 1016, in _send_output
    self.send(msg)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/http/client.py", line 956, in send
    self.connect()
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/http/client.py", line 1392, in connect
    server_hostname=server_hostname)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/ssl.py", line 412, in wrap_socket
    session=session
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/ssl.py", line 853, in _create
    self.do_handshake()
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/ssl.py", line 1117, in do_handshake
    self._sslobj.do_handshake()
ssl.SSLCertVerificationError: [SSL: CERTIFICATE_VERIFY_FAILED] certificate verify failed: unable to get local issuer certificate (_ssl.c:1056)

During handling of the above exception, another exception occurred:

Traceback (most recent call last):
  File "", line 1, in <module>
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/site-packages/Bio/Entrez/__init__.py", line 184, in efetch
    return _open(cgi, variables, post=post)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/site-packages/Bio/Entrez/__init__.py", line 543, in _open
    handle = _urlopen(cgi)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 222, in urlopen
    return opener.open(url, data, timeout)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 525, in open
    response = self._open(req, data)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 543, in _open
    '_open', req)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 503, in _call_chain
    result = func(*args)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 1360, in https_open
    context=self._context, check_hostname=self._check_hostname)
  File "/Bioinfo/Pipeline/SoftWare/Python-3.7.3/lib/python3.7/urllib/request.py", line 1319, in do_open
    raise URLError(err)
urllib.error.URLError: <urlopen error [SSL: CERTIFICATE_VERIFY_FAILED] certificate verify failed: unable to get local issuer certificate (_ssl.c:1056)>
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根据网络上的解析，当使用 urllib.urlopen 打开一个 https 链接时，会验证一次 SSL 证书。而当目标网站使用的是自签名的证书时就会抛出如下异常：

ssl.SSLCertVerificationError: [SSL: CERTIFICATE_VERIFY_FAILED] certificate verify failed: unable to get local issuer certificate (_ssl.c:1056)

解决方法也很简单，下面是个人简单总结的 3 种常用解决方法。

方法一，全局取消证书验证

>>> import ssl
>>> ssl._create_default_https_context = ssl._create_unverified_context
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方法二，指定位置安装证书

1. 查看证书默认位置。

>>> import ssl
>>> print(ssl.get_default_verify_paths())
DefaultVerifyPaths(cafile=None, capath='/Bioinfo/Pipeline/SoftWare/LibDependence/openssl-1.1.1/ssl/certs', openssl_cafile_env='SSL_CERT_FILE', openssl_cafile='/Bioinfo/Pipeline/SoftWare/LibDependence/openssl-1.1.1/ssl/cert.pem', openssl_capath_env='SSL_CERT_DIR', openssl_capath='/Bioinfo/Pipeline/SoftWare/LibDependence/openssl-1.1.1/ssl/certs')
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由于在 openssl_cafile 中指定的 ca 文件（cert.pem）不存在，所以导致上面的错误。

2. 下载 ca 文件，将下载的 ca 文件放到 openssl_cafile 指定位置。注意，如果放到 openssl_capath 目录下还会出现类似的问题，一定要放到 openssl_cafile 指定的位置。

$ cd /Bioinfo/Pipeline/SoftWare/LibDependence/openssl-1.1.1/ssl
$ wget http://curl.haxx.se/ca/cacert.pem -O cert.pem --no-check-certificate
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方法三，设置环境变量

也可以参考 stackoverflow 上的做法，通过修改下面环境变量的方式解决（亲测可行）

export SSL_CERT_FILE=/usr/local/etc/openssl/cert.pem
export REQUESTS_CA_BUNDLE=/usr/local/etc/openssl/cert.pem
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最后，问题解决。

>>> from Bio import SeqIO
>>> from Bio import Entrez
>>> Entrez.email = "A.N.Other@example.com"
>>> records = SeqIO.parse(Entrez.efetch(id='NM_001009537.4', db="nucleotide", rettype="gb", retmode="text"), "gb")
>>> for record in records:
...     for feature in record.features:
...         if feature.type == "gene":
...             print(feature.qualifiers['gene'])
...
['Zfp799']
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